Vascular Calcification: Deposition of calcium into the blood vessel structures. Excessive calcification of the vessels are associated with ATHEROSCLEROTIC PLAQUES formation particularly after MYOCARDIAL INFARCTION (see MONCKEBERG MEDIAL CALCIFIC SCLEROSIS) and chronic kidney diseases which in turn increase VASCULAR STIFFNESS.Calcinosis: Pathologic deposition of calcium salts in tissues.Vascular Diseases: Pathological processes involving any of the BLOOD VESSELS in the cardiac or peripheral circulation. They include diseases of ARTERIES; VEINS; and rest of the vasculature system in the body.Calcification, Physiologic: Process by which organic tissue becomes hardened by the physiologic deposit of calcium salts.alpha-2-HS-Glycoprotein: A fetuin subtype that is synthesized by HEPATOCYTES and secreted into the circulation. It plays a major role in preventing CALCIUM precipitation in the BLOOD.Aortic Diseases: Pathological processes involving any part of the AORTA.Hyperphosphatemia: A condition of abnormally high level of PHOSPHATES in the blood, usually significantly above the normal range of 0.84-1.58 mmol per liter of serum.Phosphates: Inorganic salts of phosphoric acid.Kidney Failure, Chronic: The end-stage of CHRONIC RENAL INSUFFICIENCY. It is characterized by the severe irreversible kidney damage (as measured by the level of PROTEINURIA) and the reduction in GLOMERULAR FILTRATION RATE to less than 15 ml per min (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002). These patients generally require HEMODIALYSIS or KIDNEY TRANSPLANTATION.Osteopontin: A negatively-charged extracellular matrix protein that plays a role in the regulation of BONE metabolism and a variety of other biological functions. Cell signaling by osteopontin may occur through a cell adhesion sequence that recognizes INTEGRIN ALPHA-V BETA-3.Osteoprotegerin: A secreted member of the TNF receptor superfamily that negatively regulates osteoclastogenesis. It is a soluble decoy receptor of RANK LIGAND that inhibits both CELL DIFFERENTIATION and function of OSTEOCLASTS by inhibiting the interaction between RANK LIGAND and RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B.Alkaline Phosphatase: An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. EC 3.1.3.1.Uremia: A clinical syndrome associated with the retention of renal waste products or uremic toxins in the blood. It is usually the result of RENAL INSUFFICIENCY. Most uremic toxins are end products of protein or nitrogen CATABOLISM, such as UREA or CREATININE. Severe uremia can lead to multiple organ dysfunctions with a constellation of symptoms.Renal Dialysis: Therapy for the insufficient cleansing of the BLOOD by the kidneys based on dialysis and including hemodialysis, PERITONEAL DIALYSIS, and HEMODIAFILTRATION.Phosphorus Metabolism Disorders: Disorders in the processing of phosphorus in the body: its absorption, transport, storage, and utilization.Monckeberg Medial Calcific Sclerosis: Thickening and loss of elasticity of the walls of muscular ARTERIES due to calcification of the TUNICA MEDIA, the concentric layers of helically arranged SMOOTH MUSCLE CELLS.Phosphorus: A non-metal element that has the atomic symbol P, atomic number 15, and atomic weight 31. It is an essential element that takes part in a broad variety of biochemical reactions.Aorta: The main trunk of the systemic arteries.Muscle, Smooth, Vascular: The nonstriated involuntary muscle tissue of blood vessels.Renal Osteodystrophy: Decalcification of bone or abnormal bone development due to chronic KIDNEY DISEASES, in which 1,25-DIHYDROXYVITAMIN D3 synthesis by the kidneys is impaired, leading to reduced negative feedback on PARATHYROID HORMONE. The resulting SECONDARY HYPERPARATHYROIDISM eventually leads to bone disorders.Calcium Carbonate: Carbonic acid calcium salt (CaCO3). An odorless, tasteless powder or crystal that occurs in nature. It is used therapeutically as a phosphate buffer in hemodialysis patients and as a calcium supplement.Diphosphates: Inorganic salts of phosphoric acid that contain two phosphate groups.Myocytes, Smooth Muscle: Non-striated, elongated, spindle-shaped cells found lining the digestive tract, uterus, and blood vessels. They are derived from specialized myoblasts (MYOBLASTS, SMOOTH MUSCLE).Renal Insufficiency, Chronic: Conditions in which the KIDNEYS perform below the normal level for more than three months. Chronic kidney insufficiency is classified by five stages according to the decline in GLOMERULAR FILTRATION RATE and the degree of kidney damage (as measured by the level of PROTEINURIA). The most severe form is the end-stage renal disease (CHRONIC KIDNEY FAILURE). (Kidney Foundation: Kidney Disease Outcome Quality Initiative, 2002)Hyperparathyroidism, Secondary: Abnormally elevated PARATHYROID HORMONE secretion as a response to HYPOCALCEMIA. It is caused by chronic KIDNEY FAILURE or other abnormalities in the controls of bone and mineral metabolism, leading to various BONE DISEASES, such as RENAL OSTEODYSTROPHY.Kidney Diseases: Pathological processes of the KIDNEY or its component tissues.Atherosclerosis: A thickening and loss of elasticity of the walls of ARTERIES that occurs with formation of ATHEROSCLEROTIC PLAQUES within the ARTERIAL INTIMA.Osteogenesis: The process of bone formation. Histogenesis of bone including ossification.Bone Diseases, Endocrine: Diseases of the bones related to hyperfunction or hypofunction of the endocrine glands.Core Binding Factor Alpha 1 Subunit: A transcription factor that dimerizes with CORE BINDING FACTOR BETA SUBUNIT to form core binding factor. It contains a highly conserved DNA-binding domain known as the runt domain and is involved in genetic regulation of skeletal development and CELL DIFFERENTIATION.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., COLLAGEN; ELASTIN; FIBRONECTINS; and LAMININ).Tomography, X-Ray Computed: Tomography using x-ray transmission and a computer algorithm to reconstruct the image.Calcium-Binding Proteins: Proteins to which calcium ions are bound. They can act as transport proteins, regulator proteins, or activator proteins. They typically contain EF HAND MOTIFS.Sialoglycoproteins: Glycoproteins which contain sialic acid as one of their carbohydrates. They are often found on or in the cell or tissue membranes and participate in a variety of biological activities.Minerals: Native, inorganic or fossilized organic substances having a definite chemical composition and formed by inorganic reactions. They may occur as individual crystals or may be disseminated in some other mineral or rock. (Grant & Hackh's Chemical Dictionary, 5th ed; McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Thiosulfates: Inorganic salts of thiosulfuric acid possessing the general formula R2S2O3.Sodium-Phosphate Cotransporter Proteins, Type III: A family of highly conserved and widely expressed sodium-phosphate cotransporter proteins. They are electrogenic sodium-dependent transporters of phosphate that were originally identified as retroviral receptors in HUMANS and have been described in yeast and many other organisms.Heart Valve Diseases: Pathological conditions involving any of the various HEART VALVES and the associated structures (PAPILLARY MUSCLES and CHORDAE TENDINEAE).Blood Vessels: Any of the tubular vessels conveying the blood (arteries, arterioles, capillaries, venules, and veins).Calciphylaxis: Condition of induced systemic hypersensitivity in which tissues respond to appropriate challenging agents with a sudden local calcification.PolyaminesOsteoblasts: Bone-forming cells which secrete an EXTRACELLULAR MATRIX. HYDROXYAPATITE crystals are then deposited into the matrix to form bone.Polyethylenes: Synthetic thermoplastics that are tough, flexible, inert, and resistant to chemicals and electrical current. They are often used as biocompatible materials for prostheses and implants.Vitamin D: A vitamin that includes both CHOLECALCIFEROLS and ERGOCALCIFEROLS, which have the common effect of preventing or curing RICKETS in animals. It can also be viewed as a hormone since it can be formed in SKIN by action of ULTRAVIOLET RAYS upon the precursors, 7-dehydrocholesterol and ERGOSTEROL, and acts on VITAMIN D RECEPTORS to regulate CALCIUM in opposition to PARATHYROID HORMONE.Coronary Artery Disease: Pathological processes of CORONARY ARTERIES that may derive from a congenital abnormality, atherosclerotic, or non-atherosclerotic cause.Bone Morphogenetic Protein 2: A potent osteoinductive protein that plays a critical role in the differentiation of osteoprogenitor cells into OSTEOBLASTS.Arteries: The vessels carrying blood away from the heart.Parathyroid Hormone: A polypeptide hormone (84 amino acid residues) secreted by the PARATHYROID GLANDS which performs the essential role of maintaining intracellular CALCIUM levels in the body. Parathyroid hormone increases intracellular calcium by promoting the release of CALCIUM from BONE, increases the intestinal absorption of calcium, increases the renal tubular reabsorption of calcium, and increases the renal excretion of phosphates.Chronic Disease: Diseases which have one or more of the following characteristics: they are permanent, leave residual disability, are caused by nonreversible pathological alteration, require special training of the patient for rehabilitation, or may be expected to require a long period of supervision, observation, or care. (Dictionary of Health Services Management, 2d ed)Etidronic Acid: A diphosphonate which affects calcium metabolism. It inhibits ectopic calcification and slows down bone resorption and bone turnover.Aorta, Abdominal: The aorta from the DIAPHRAGM to the bifurcation into the right and left common iliac arteries.RANK Ligand: A transmembrane protein belonging to the tumor necrosis factor superfamily that specifically binds RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B and OSTEOPROTEGERIN. It plays an important role in regulating OSTEOCLAST differentiation and activation.Ergocalciferols: Derivatives of ERGOSTEROL formed by ULTRAVIOLET RAYS breaking of the C9-C10 bond. They differ from CHOLECALCIFEROL in having a double bond between C22 and C23 and a methyl group at C24.Risk Factors: An aspect of personal behavior or lifestyle, environmental exposure, or inborn or inherited characteristic, which, on the basis of epidemiologic evidence, is known to be associated with a health-related condition considered important to prevent.Osteocalcin: Vitamin K-dependent calcium-binding protein synthesized by OSTEOBLASTS and found primarily in BONES. Serum osteocalcin measurements provide a noninvasive specific marker of bone metabolism. The protein contains three residues of the amino acid gamma-carboxyglutamic acid (Gla), which, in the presence of CALCIUM, promotes binding to HYDROXYAPATITE and subsequent accumulation in BONE MATRIX.Aorta, Thoracic: The portion of the descending aorta proceeding from the arch of the aorta and extending to the DIAPHRAGM, eventually connecting to the ABDOMINAL AORTA.Glycerophosphates: Any salt or ester of glycerophosphoric acid.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Plaque, Atherosclerotic: Lesions formed within the walls of ARTERIES.Bone and Bones: A specialized CONNECTIVE TISSUE that is the main constituent of the SKELETON. The principle cellular component of bone is comprised of OSTEOBLASTS; OSTEOCYTES; and OSTEOCLASTS, while FIBRILLAR COLLAGENS and hydroxyapatite crystals form the BONE MATRIX.Tomography, Spiral Computed: Computed tomography where there is continuous X-ray exposure to the patient while being transported in a spiral or helical pattern through the beam of irradiation. This provides improved three-dimensional contrast and spatial resolution compared to conventional computed tomography, where data is obtained and computed from individual sequential exposures.Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis (OSTEOPOROSIS, POSTMENOPAUSAL) and age-related or senile osteoporosis.Arteriosclerosis: Thickening and loss of elasticity of the walls of ARTERIES of all sizes. There are many forms classified by the types of lesions and arteries involved, such as ATHEROSCLEROSIS with fatty lesions in the ARTERIAL INTIMA of medium and large muscular arteries.Cardiovascular Diseases: Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.Vitamin K: A lipid cofactor that is required for normal blood clotting. Several forms of vitamin K have been identified: VITAMIN K 1 (phytomenadione) derived from plants, VITAMIN K 2 (menaquinone) from bacteria, and synthetic naphthoquinone provitamins, VITAMIN K 3 (menadione). Vitamin K 3 provitamins, after being alkylated in vivo, exhibit the antifibrinolytic activity of vitamin K. Green leafy vegetables, liver, cheese, butter, and egg yolk are good sources of vitamin K.Bone Diseases: Diseases of BONES.Mice, Knockout: Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.Bone Morphogenetic Protein 7: A bone morphogenetic protein that is widely expressed during EMBRYONIC DEVELOPMENT. It is both a potent osteogenic factor and a specific regulator of nephrogenesis.Calcitriol: The physiologically active form of vitamin D. It is formed primarily in the kidney by enzymatic hydroxylation of 25-hydroxycholecalciferol (CALCIFEDIOL). Its production is stimulated by low blood calcium levels and parathyroid hormone. Calcitriol increases intestinal absorption of calcium and phosphorus, and in concert with parathyroid hormone increases bone resorption.Calcium Compounds: Inorganic compounds that contain calcium as an integral part of the molecule.Calcium Phosphates: Calcium salts of phosphoric acid. These compounds are frequently used as calcium supplements.Cholecalciferol: Derivative of 7-dehydroxycholesterol formed by ULTRAVIOLET RAYS breaking of the C9-C10 bond. It differs from ERGOCALCIFEROL in having a single bond between C22 and C23 and lacking a methyl group at C24.Fibroblast Growth Factors: A family of small polypeptide growth factors that share several common features including a strong affinity for HEPARIN, and a central barrel-shaped core region of 140 amino acids that is highly homologous between family members. Although originally studied as proteins that stimulate the growth of fibroblasts this distinction is no longer a requirement for membership in the fibroblast growth factor family.Disease Progression: The worsening of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis.Bone Morphogenetic Proteins: Bone-growth regulatory factors that are members of the transforming growth factor-beta superfamily of proteins. They are synthesized as large precursor molecules which are cleaved by proteolytic enzymes. The active form can consist of a dimer of two identical proteins or a heterodimer of two related bone morphogenetic proteins.GlucuronidaseLevamisole: An antihelminthic drug that has been tried experimentally in rheumatic disorders where it apparently restores the immune response by increasing macrophage chemotaxis and T-lymphocyte function. Paradoxically, this immune enhancement appears to be beneficial in rheumatoid arthritis where dermatitis, leukopenia, and thrombocytopenia, and nausea and vomiting have been reported as side effects. (From Smith and Reynard, Textbook of Pharmacology, 1991, p435-6)Dental Pulp CalcificationTunica Media: The middle layer of blood vessel walls, composed principally of thin, cylindrical, smooth muscle cells and elastic tissue. It accounts for the bulk of the wall of most arteries. The smooth muscle cells are arranged in circular layers around the vessel, and the thickness of the coat varies with the size of the vessel.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.Epoxy Compounds: Organic compounds that include a cyclic ether with three ring atoms in their structure. They are commonly used as precursors for POLYMERS such as EPOXY RESINS.Calcimimetic Agents: Small organic molecules that act as allosteric activators of the calcium sensing receptor (CaSR) in the PARATHYROID GLANDS and other tissues. They lower the threshold for CaSR activation by extracellular calcium ions and diminish PARATHYROID HORMONE (PTH) release from parathyroid cells.Tropoelastin: A salt-soluble precursor of elastin. Lysyl oxidase is instrumental in converting it to elastin in connective tissue.Brachiocephalic Trunk: The first and largest artery branching from the aortic arch. It distributes blood to the right side of the head and neck and to the right arm.Durapatite: The mineral component of bones and teeth; it has been used therapeutically as a prosthetic aid and in the prevention and treatment of osteoporosis.Vitamin K 1: A family of phylloquinones that contains a ring of 2-methyl-1,4-naphthoquinone and an isoprenoid side chain. Members of this group of vitamin K 1 have only one double bond on the proximal isoprene unit. Rich sources of vitamin K 1 include green plants, algae, and photosynthetic bacteria. Vitamin K1 has antihemorrhagic and prothrombogenic activity.Aortic Valve: The valve between the left ventricle and the ascending aorta which prevents backflow into the left ventricle.Receptor Activator of Nuclear Factor-kappa B: A tumor necrosis factor receptor family member that is specific for RANK LIGAND and plays a role in bone homeostasis by regulating osteoclastogenesis. It is also expressed on DENDRITIC CELLS where it plays a role in regulating dendritic cell survival. Signaling by the activated receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.Warfarin: An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide.ElastinChelating Agents: Chemicals that bind to and remove ions from solutions. Many chelating agents function through the formation of COORDINATION COMPLEXES with METALS.Severity of Illness Index: Levels within a diagnostic group which are established by various measurement criteria applied to the seriousness of a patient's disorder.Cattle: Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.Cell Transdifferentiation: A naturally occurring phenomenon where terminally differentiated cells dedifferentiate to the point where they can switch CELL LINEAGES. The cells then differentiate into other cell types.Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Receptors, LDL: Receptors on the plasma membrane of nonhepatic cells that specifically bind LDL. The receptors are localized in specialized regions called coated pits. Hypercholesteremia is caused by an allelic genetic defect of three types: 1, receptors do not bind to LDL; 2, there is reduced binding of LDL; and 3, there is normal binding but no internalization of LDL. In consequence, entry of cholesterol esters into the cell is impaired and the intracellular feedback by cholesterol on 3-hydroxy-3-methylglutaryl CoA reductase is lacking.Phosphorus, Dietary: Phosphorus used in foods or obtained from food. This element is a major intracellular component which plays an important role in many biochemical pathways relating to normal physiological functions. High concentrations of dietary phosphorus can cause nephrocalcinosis which is associated with impaired kidney function. Low concentrations of dietary phosphorus cause an increase in calcitriol in the blood and osteoporosis.Coronary Vessels: The veins and arteries of the HEART.Bone Density: The amount of mineral per square centimeter of BONE. This is the definition used in clinical practice. Actual bone density would be expressed in grams per milliliter. It is most frequently measured by X-RAY ABSORPTIOMETRY or TOMOGRAPHY, X RAY COMPUTED. Bone density is an important predictor for OSTEOPOROSIS.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Bone Diseases, MetabolicBone Remodeling: The continuous turnover of BONE MATRIX and mineral that involves first an increase in BONE RESORPTION (osteoclastic activity) and later, reactive BONE FORMATION (osteoblastic activity). The process of bone remodeling takes place in the adult skeleton at discrete foci. The process ensures the mechanical integrity of the skeleton throughout life and plays an important role in calcium HOMEOSTASIS. An imbalance in the regulation of bone remodeling's two contrasting events, bone resorption and bone formation, results in many of the metabolic bone diseases, such as OSTEOPOROSIS.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Apolipoproteins E: A class of protein components which can be found in several lipoproteins including HIGH-DENSITY LIPOPROTEINS; VERY-LOW-DENSITY LIPOPROTEINS; and CHYLOMICRONS. Synthesized in most organs, Apo E is important in the global transport of lipids and cholesterol throughout the body. Apo E is also a ligand for LDL receptors (RECEPTORS, LDL) that mediates the binding, internalization, and catabolism of lipoprotein particles in cells. There are several allelic isoforms (such as E2, E3, and E4). Deficiency or defects in Apo E are causes of HYPERLIPOPROTEINEMIA TYPE III.Blood Proteins: Proteins that are present in blood serum, including SERUM ALBUMIN; BLOOD COAGULATION FACTORS; and many other types of proteins.Hyperparathyroidism: A condition of abnormally elevated output of PARATHYROID HORMONE (or PTH) triggering responses that increase blood CALCIUM. It is characterized by HYPERCALCEMIA and BONE RESORPTION, eventually leading to bone diseases. PRIMARY HYPERPARATHYROIDISM is caused by parathyroid HYPERPLASIA or PARATHYROID NEOPLASMS. SECONDARY HYPERPARATHYROIDISM is increased PTH secretion in response to HYPOCALCEMIA, usually caused by chronic KIDNEY DISEASES.Peritoneal Dialysis: Dialysis fluid being introduced into and removed from the peritoneal cavity as either a continuous or an intermittent procedure.Mice, Inbred C57BLFemoral Artery: The main artery of the thigh, a continuation of the external iliac artery.Receptors, Calcitriol: Proteins, usually found in the cytoplasm, that specifically bind calcitriol, migrate to the nucleus, and regulate transcription of specific segments of DNA with the participation of D receptor interacting proteins (called DRIP). Vitamin D is converted in the liver and kidney to calcitriol and ultimately acts through these receptors.Basal Ganglia Diseases: Diseases of the BASAL GANGLIA including the PUTAMEN; GLOBUS PALLIDUS; claustrum; AMYGDALA; and CAUDATE NUCLEUS. DYSKINESIAS (most notably involuntary movements and alterations of the rate of movement) represent the primary clinical manifestations of these disorders. Common etiologies include CEREBROVASCULAR DISORDERS; NEURODEGENERATIVE DISEASES; and CRANIOCEREBRAL TRAUMA.Tunica Intima: The innermost layer of an artery or vein, made up of one layer of endothelial cells and supported by an internal elastic lamina.Receptors, Calcium-Sensing: A class of G-protein-coupled receptors that react to varying extracellular CALCIUM levels. Calcium-sensing receptors in the PARATHYROID GLANDS play an important role in the maintenance of calcium HOMEOSTASIS by regulating the release of PARATHYROID HORMONE. They differ from INTRACELLULAR CALCIUM-SENSING PROTEINS which sense intracellular calcium levels.Bone Development: The growth and development of bones from fetus to adult. It includes two principal mechanisms of bone growth: growth in length of long bones at the epiphyseal cartilages and growth in thickness by depositing new bone (OSTEOGENESIS) with the actions of OSTEOBLASTS and OSTEOCLASTS.Lanthanum: Lanthanum. The prototypical element in the rare earth family of metals. It has the atomic symbol La, atomic number 57, and atomic weight 138.91. Lanthanide ion is used in experimental biology as a calcium antagonist; lanthanum oxide improves the optical properties of glass.Naphthalenes: Two-ring crystalline hydrocarbons isolated from coal tar. They are used as intermediates in chemical synthesis, as insect repellents, fungicides, lubricants, preservatives, and, formerly, as topical antiseptics.Diabetic Angiopathies: VASCULAR DISEASES that are associated with DIABETES MELLITUS.Up-Regulation: A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.Progeria: An abnormal congenital condition, associated with defects in the LAMIN TYPE A gene, which is characterized by premature aging in children, where all the changes of cell senescence occur. It is manifested by premature greying; hair loss; hearing loss (DEAFNESS); cataracts (CATARACT); ARTHRITIS; OSTEOPOROSIS; DIABETES MELLITUS; atrophy of subcutaneous fat; skeletal hypoplasia; elevated urinary HYALURONIC ACID; and accelerated ATHEROSCLEROSIS. Many affected individuals develop malignant tumors, especially SARCOMA.Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group.Peripheral Vascular Diseases: Pathological processes involving any one of the BLOOD VESSELS in the vasculature outside the HEART.Drug Antagonism: Phenomena and pharmaceutics of compounds that inhibit the function of agonists (DRUG AGONISM) and inverse agonists (DRUG INVERSE AGONISM) for a specific receptor. On their own, antagonists produce no effect by themselves to a receptor, and are said to have neither intrinsic activity nor efficacy.Aortic Valve Stenosis: A pathological constriction that can occur above (supravalvular stenosis), below (subvalvular stenosis), or at the AORTIC VALVE. It is characterized by restricted outflow from the LEFT VENTRICLE into the AORTA.Risk Assessment: The qualitative or quantitative estimation of the likelihood of adverse effects that may result from exposure to specified health hazards or from the absence of beneficial influences. (Last, Dictionary of Epidemiology, 1988)Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from INCIDENCE, which refers to the number of new cases in the population at a given time.Carotid Arteries: Either of the two principal arteries on both sides of the neck that supply blood to the head and neck; each divides into two branches, the internal carotid artery and the external carotid artery.Activating Transcription Factor 4: An activating transcription factor that regulates the expression of a variety of GENES involved in amino acid metabolism and transport. It also interacts with HTLV-I transactivator protein.Cross-Sectional Studies: Studies in which the presence or absence of disease or other health-related variables are determined in each member of the study population or in a representative sample at one particular time. This contrasts with LONGITUDINAL STUDIES which are followed over a period of time.Bone Density Conservation Agents: Agents that inhibit BONE RESORPTION and/or favor BONE MINERALIZATION and BONE REGENERATION. They are used to heal BONE FRACTURES and to treat METABOLIC BONE DISEASES such as OSTEOPOROSIS.Osteoclasts: A large multinuclear cell associated with the BONE RESORPTION. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in CEMENTUM resorption.Anthozoa: A class in the phylum CNIDARIA, comprised mostly of corals and anemones. All members occur only as polyps; the medusa stage is completely absent.Ossification, Heterotopic: The development of bony substance in normally soft structures.Follow-Up Studies: Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease.Predictive Value of Tests: In screening and diagnostic tests, the probability that a person with a positive test is a true positive (i.e., has the disease), is referred to as the predictive value of a positive test; whereas, the predictive value of a negative test is the probability that the person with a negative test does not have the disease. Predictive value is related to the sensitivity and specificity of the test.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Kidney Transplantation: The transference of a kidney from one human or animal to another.Chi-Square Distribution: A distribution in which a variable is distributed like the sum of the squares of any given independent random variable, each of which has a normal distribution with mean of zero and variance of one. The chi-square test is a statistical test based on comparison of a test statistic to a chi-square distribution. The oldest of these tests are used to detect whether two or more population distributions differ from one another.C-Reactive Protein: A plasma protein that circulates in increased amounts during inflammation and after tissue damage.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Vitamin D Deficiency: A nutritional condition produced by a deficiency of VITAMIN D in the diet, insufficient production of vitamin D in the skin, inadequate absorption of vitamin D from the diet, or abnormal conversion of vitamin D to its bioactive metabolites. It is manifested clinically as RICKETS in children and OSTEOMALACIA in adults. (From Cecil Textbook of Medicine, 19th ed, p1406)Diphosphonates: Organic compounds which contain P-C-P bonds, where P stands for phosphonates or phosphonic acids. These compounds affect calcium metabolism. They inhibit ectopic calcification and slow down bone resorption and bone turnover. Technetium complexes of diphosphonates have been used successfully as bone scanning agents.Cohort Studies: Studies in which subsets of a defined population are identified. These groups may or may not be exposed to factors hypothesized to influence the probability of the occurrence of a particular disease or other outcome. Cohorts are defined populations which, as a whole, are followed in an attempt to determine distinguishing subgroup characteristics.Sensitivity and Specificity: Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)Bioprosthesis: Prosthesis, usually heart valve, composed of biological material and whose durability depends upon the stability of the material after pretreatment, rather than regeneration by host cell ingrowth. Durability is achieved 1, mechanically by the interposition of a cloth, usually polytetrafluoroethylene, between the host and the graft, and 2, chemically by stabilization of the tissue by intermolecular linking, usually with glutaraldehyde, after removal of antigenic components, or the use of reconstituted and restructured biopolymers.Pseudoxanthoma Elasticum: An inherited disorder of connective tissue with extensive degeneration and calcification of ELASTIC TISSUE primarily in the skin, eye, and vasculature. At least two forms exist, autosomal recessive and autosomal dominant. This disorder is caused by mutations of one of the ATP-BINDING CASSETTE TRANSPORTERS. Patients are predisposed to MYOCARDIAL INFARCTION and GASTROINTESTINAL HEMORRHAGE.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Mitral Valve: The valve between the left atrium and left ventricle of the heart.Elasticity: Resistance and recovery from distortion of shape.Vitamins: Organic substances that are required in small amounts for maintenance and growth, but which cannot be manufactured by the human body.S100 Proteins: A family of highly acidic calcium-binding proteins found in large concentration in the brain and believed to be glial in origin. They are also found in other organs in the body. They have in common the EF-hand motif (EF HAND MOTIFS) found on a number of calcium binding proteins. The name of this family derives from the property of being soluble in a 100% saturated ammonium sulfate solution.Cardiomyopathies: A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).Glutaral: One of the protein CROSS-LINKING REAGENTS that is used as a disinfectant for sterilization of heat-sensitive equipment and as a laboratory reagent, especially as a fixative.Receptors, Cytoplasmic and Nuclear: Intracellular receptors that can be found in the cytoplasm or in the nucleus. They bind to extracellular signaling molecules that migrate through or are transported across the CELL MEMBRANE. Many members of this class of receptors occur in the cytoplasm and are transported to the CELL NUCLEUS upon ligand-binding where they signal via DNA-binding and transcription regulation. Also included in this category are receptors found on INTRACELLULAR MEMBRANES that act via mechanisms similar to CELL SURFACE RECEPTORS.Retrospective Studies: Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons.Brain Diseases: Pathologic conditions affecting the BRAIN, which is composed of the intracranial components of the CENTRAL NERVOUS SYSTEM. This includes (but is not limited to) the CEREBRAL CORTEX; intracranial white matter; BASAL GANGLIA; THALAMUS; HYPOTHALAMUS; BRAIN STEM; and CEREBELLUM.Nephrocalcinosis: A condition characterized by calcification of the renal tissue itself. It is usually seen in distal RENAL TUBULAR ACIDOSIS with calcium deposition in the DISTAL KIDNEY TUBULES and the surrounding interstitium. Nephrocalcinosis causes RENAL INSUFFICIENCY.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Age Factors: Age as a constituent element or influence contributing to the production of a result. It may be applicable to the cause or the effect of a circumstance. It is used with human or animal concepts but should be differentiated from AGING, a physiological process, and TIME FACTORS which refers only to the passage of time.Tooth Calcification: The process whereby calcium salts are deposited in the dental enamel. The process is normal in the development of bones and teeth. (Boucher's Clinical Dental Terminology, 4th ed, p43)Prognosis: A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.Kidney: Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.Glomerular Filtration Rate: The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to INULIN clearance.Carbonates: Salts or ions of the theoretical carbonic acid, containing the radical CO2(3-). Carbonates are readily decomposed by acids. The carbonates of the alkali metals are water-soluble; all others are insoluble. (From Grant & Hackh's Chemical Dictionary, 5th ed)Pyrophosphatases: A group of enzymes within the class EC 3.6.1.- that catalyze the hydrolysis of diphosphate bonds, chiefly in nucleoside di- and triphosphates. They may liberate either a mono- or diphosphate. EC 3.6.1.-.Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.Diabetes Mellitus: A heterogeneous group of disorders characterized by HYPERGLYCEMIA and GLUCOSE INTOLERANCE.Bone Matrix: Extracellular substance of bone tissue consisting of COLLAGEN fibers, ground substance, and inorganic crystalline minerals and salts.Logistic Models: Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a given risk factor.Diet, High-Fat: Consumption of excessive DIETARY FATS.Receptors, Tumor Necrosis Factor: Cell surface receptors that bind TUMOR NECROSIS FACTORS and trigger changes which influence the behavior of cells.Intercellular Signaling Peptides and Proteins: Regulatory proteins and peptides that are signaling molecules involved in the process of PARACRINE COMMUNICATION. They are generally considered factors that are expressed by one cell and are responded to by receptors on another nearby cell. They are distinguished from HORMONES in that their actions are local rather than distal.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Scleral Diseases: General disorders of the sclera or white of the eye. They may include anatomic, embryologic, degenerative, or pigmentation defects.Models, Biological: Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.Transcription Factor CHOP: A CCAAT-enhancer binding protein that is induced by DNA DAMAGE and growth arrest. It serves as a dominant negative inhibitor of other CCAAT-enhancer binding proteins.Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function.Kidney Function Tests: Laboratory tests used to evaluate how well the kidneys are working through examination of blood and urine.Chondrocalcinosis: Presence of calcium salts, especially calcium pyrophosphate, in the cartilaginous structures of one or more joints. When accompanied by attacks of goutlike symptoms, it is called pseudogout. (Dorland, 27th ed)Reproducibility of Results: The statistical reproducibility of measurements (often in a clinical context), including the testing of instrumentation or techniques to obtain reproducible results. The concept includes reproducibility of physiological measurements, which may be used to develop rules to assess probability or prognosis, or response to a stimulus; reproducibility of occurrence of a condition; and reproducibility of experimental results.Carotid Artery Diseases: Pathological conditions involving the CAROTID ARTERIES, including the common, internal, and external carotid arteries. ATHEROSCLEROSIS and TRAUMA are relatively frequent causes of carotid artery pathology.Homeodomain Proteins: Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (GENE EXPRESSION REGULATION, DEVELOPMENTAL).Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.Dietary Supplements: Products in capsule, tablet or liquid form that provide dietary ingredients, and that are intended to be taken by mouth to increase the intake of nutrients. Dietary supplements can include macronutrients, such as proteins, carbohydrates, and fats; and/or MICRONUTRIENTS, such as VITAMINS; MINERALS; and PHYTOCHEMICALS.Cartilage: A non-vascular form of connective tissue composed of CHONDROCYTES embedded in a matrix that includes CHONDROITIN SULFATE and various types of FIBRILLAR COLLAGEN. There are three major types: HYALINE CARTILAGE; FIBROCARTILAGE; and ELASTIC CARTILAGE.Apatites: A group of phosphate minerals that includes ten mineral species and has the general formula X5(YO4)3Z, where X is usually calcium or lead, Y is phosphorus or arsenic, and Z is chlorine, fluorine, or OH-. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
Mice that lack MGP develop to term but die within two months as a result of arterial calcification which leads to blood-vessel ... "A role for the endothelium in vascular calcification". Circ. Res. 113 (5): 495-504. doi:10.1161/CIRCRESAHA.113.301792. PMC ... "Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein". Nature. 386 (6620): 78-81. doi:10.1038 ... The protein acts as an inhibitor of vascular mineralization and plays a role in bone organization. MGP is found in number body ...
... "dystrophic calcification". Fetuin-A deficiency dramatically increased the calcification proneness of these mice in that all ... Fetuin-A was originally discovered to be an inhibitor of vascular calcification in early 1990s. Since then the biologic roles ... Feeding a mineral-rich diet to fetuin-A-deficient mice resulted in widespread calcification (ectopic mineralization) of lung, ... heart, and kidneys in these mice. The calcification became drastically exacerbated when the fetuin-A knockout was combined with ...
"Increased dietary intake of vitamin A promotes aortic valve calcification in vivo". Arteriosclerosis, Thrombosis, and Vascular ... Hypervitaminosis A causes hypothyroidism in mice. These treatments have been used to help treat or manage toxicity in animals. ... Sharma RL, Sharma N (February 2016). "Hypervitaminosis-A, Causes Hypothyroidism in Mouse". The International Journal of Science ... "Polyenephosphatidylcholine prevents alcoholic liver disease in PPARalpha-null mice through attenuation of increases in ...
... parathyroid hormone and vascular calcification in uremia". Blood Purification. 20 (5): 494-7. doi:10.1159/000065203. PMID ... Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta ... A conditional knockout mouse line called Pthtm1a(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute. Male and ... Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9-13. doi:10.1016/j.cell.2006.12.018. PMID ...
... which enhance vascular reactivity and reduce vascular calcification in a mouse model of atherosclerosis, as well as improving ... "Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice". Aging Cell. doi: ... cardiovascular function in old mice. There are a variety of types of surgery: Angioplasty and stent placement: A catheter is ...
Extensive diffuse cartilaginous calcification is present in MGP-knockout mice, manifesting in vascular media replacement with a ... "Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein". Nature. 386 (6620): 78-81. Bibcode: ... as a biomarker for cardiovascular calcification". Journal of Vascular Research. 45 (5): 427-436. doi:10.1159/000124863. PMID ... patients develop significant arterial calcification throughout the body. Such calcification is concomitant with various ...
In mice, decrease of B-catenin results in a decrease in the proliferation of CNCCs. Downregulation of the Wnt coreceptor Lrp6 ... In humans, mutations in Notch most often result in bicuspid aortic valve disease and calcification of the aortic valve. Bone ... The CNCCs themselves are the precursors to vascular smooth muscle cells and cardiac neurons. For example, CNCCs are required ... FGF8 mouse mutants have a range of cardiac defects including underdeveloped arch arteries and transposition of the great ...
Sharp J (March 1954). "Heredo-familial vascular and articular calcification". Annals of the Rheumatic Diseases. 13 (1): 15-27. ... "Mouse PubMed Reference:". Misumi Y, Ogata S, Ohkubo K, Hirose S, Ikehara Y (August 1990). "Primary structure of human placental ... Rare allelic variants are associated with a syndrome of adult-onset calcification of joints and arteries (CALJA) affecting the ... "NT5E mutations and arterial calcifications". The New England Journal of Medicine. 364 (5): 432-42. doi:10.1056/NEJMoa0912923. ...
... as inhibition of the channel causes a decrease in vascular calcification. Over-expression of these channels has quite a ... The knockout mice also experienced intention tremors, shorter stride length, and slower swim speed. All of these are symptoms ... In doing so it was observed that there were changes in the blood vessels of the mice. The animals without the BK channels ... Studies have shown that this treatment causes proliferation of vascular smooth muscle cells. This finding has sparked further ...
Drüeke TB, Massy ZA (2003). "Advanced oxidation protein products, parathyroid hormone and vascular calcification in uremia". ... Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta ... "International Mouse Phenotyping Consortium".. *^ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, ... "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.. ...
2000). "Phosphate regulation of vascular smooth muscle cell calcification". Circ. Res. 87 (7): E10-7. doi:10.1161/01.RES.87.7. ... 2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci ... in vascular smooth muscle cell calcification". Circ. Res. 98 (7): 905-12. doi:10.1161/01.RES.0000216409.20863.e7. PMID 16527991 ... "Mouse PubMed Reference:". Kavanaugh MP, Miller DG, Zhang W, Law W, Kozak SL, Kabat D, Miller AD (Aug 1994). "Cell-surface ...
"The good and the bad in the link between insulin resistance and vascular calcification". Atherosclerosis. 193 (2): 241-4. doi: ... "Mouse PubMed Reference:". Funakoshi I, Kato H, Horie K, Yano T, Hori Y, Kobayashi H, Inoue T, Suzuki H, Fukui S, Tsukahara M ( ... Mutations in this gene have been associated with Idiopathic infantile arterial calcification, ossification of the posterior ... "PC-1 nucleoside triphosphate pyrophosphohydrolase deficiency in idiopathic infantile arterial calcification". Am. J. Pathol. ...
Thus fetuin-A is a potent inhibitor of pathological calcification. Mice deficient in fetuin-A show systemic calcification of ... 2003). "Novel insights into uremic vascular calcification: role of matrix Gla protein and alpha-2-Heremans Schmid glycoprotein/ ... prevents extraosseous calcification induced by uraemia and phosphate challenge in mice". Nephrol. Dial. Transplant. 22 (6): ... Ketteler M (2005). "Fetuin-A and extraosseous calcification in uremia". Curr. Opin. Nephrol. Hypertens. 14 (4): 337-42. doi: ...
Calcification forms among vascular smooth muscle cells of the surrounding muscular layer, specifically in the muscle cells ... The sugar, cyclodextrin, removed cholesterol that had built up in the arteries of mice fed a high-fat diet. Aging is the most ... In addition, the calcification deposits between the outer portion of the atheroma and the muscular wall, as they progress, lead ... Vascular bypass surgery can re-establish flow around the diseased segment of artery, and angioplasty with or without stenting ...
The phenotype of knock out mice demonstrates that pdgfrb is essential for vascular development, and that pdgfb is responsible ... Primary familial brain calcification (see Fahr's syndrome) is a rare disease involving bilateral calcifications in the brain, ... Mice harboring a single activated allele of pdgfrb show a number of postnatal phenotypes including reduced differentiation of ... Levéen P, Pekny M, Gebre-Medhin S, Swolin B, Larsson E, Betsholtz C (1994). "Mice deficient for PDGF B show renal, ...
Li X, Giachelli CM (2007). "Sodium-dependent phosphate cotransporters and vascular calcification". Curr. Opin. Nephrol. ... "Mouse PubMed Reference:". "Entrez Gene: POU1F1 POU domain, class 1, transcription factor 1 (Pit1, growth hormone factor 1)". ...
In vascular smooth muscle cell (VSMC), ADAMTS7 mediates VSMC migration, which plays an essential role during the development of ... Significant associations for coronary artery calcification with SNPs in ADAMTS7 has also been found in Hispanics. Additionally ... Adamts7 deficiency in both the Ldlr−/− and Apoe−/− hyperlipidemic mouse models markedly attenuates formation of atherosclerotic ... "ADAMTS-7 mediates vascular smooth muscle cell migration and neointima formation in balloon-injured rat arteries". Circulation ...
"Increased dietary intake of vitamin A promotes aortic valve calcification in vivo". Arteriosclerosis, Thrombosis, and Vascular ... Hypervitaminosis A causes hypothyroidism in mice.[42]. TreatmentEdit. These treatments have been used to help treat or manage ... "Hypervitaminosis-A, Causes Hypothyroidism in Mouse". The International Journal of Science and Technoledge. 4 (2): 62-4. ... "Polyenephosphatidylcholine prevents alcoholic liver disease in PPARalpha-null mice through attenuation of increases in ...
Mouse models where the Jag1 gene is turned off in certain tissues (conditional knockout mouse models) have been used to study ... kidneys and vascular system. The most clinically significant concerns stem from liver, heart, vascular or renal problems. ... "Endothelial deletion of murine Jag1 leads to valve calcification and congenital heart defects associated with Alagille syndrome ... mice haploinsufficient for both Jag1 and Notch2 present with the ALGS phenotype. Conditional gene knockout mouse models with ...
Mice fed a high cholesterol diet showed significantly more vascular damage and hypertension when they had been infected with ... Another 5% later develop cerebral calcification (decreasing IQ levels dramatically and causing sensorineural deafness and ... A study published in 2009 links infection with CMV to high blood pressure in mice, and suggests that the result of CMV ... CMV infection stimulated cytokines - IL6, TNF, and MCP1 - in the infected mice, indicating that the infection led to an ...
The enzyme activity was detected in rabbits, mice and rats, and humans, and it is now believed to be ubiquitous in vertebrates ... The EETs display different properties in different vascular beds. The DHETs are more readily excreted, but they have yet to be ... R287Q was associated with coronary artery calcification in African American population participating in the CARDIA study. The ... The sEH was first identified in the cytosolic fraction of mouse liver through its activity on epoxide containing substrates ...
"Sortilin mediates vascular calcification via its recruitment into extracellular vesicles". The Journal of Clinical ... "Mouse PubMed Reference:". "Entrez Gene: SORT1 sortilin 1". "BioGPS - your Gene Portal System". biogps.org. Retrieved 2016-08-16 ...
However recent models in mice show that the dysfunction in the cerebellum may play an equal part in dystonia. . Hemiballismus ... Though there are known causes of dystonia such as metabolic, vascular, and structural abnormalities, there are still patients ... There is physiological intracranial calcification in about 0,3-1,5% of individuals. Fahr's disease is a rare, genetically ... Basal ganglia calcification: clinical manifestations and diagnostic evaluation]". Georgian Med News (in Russian) (140): 39-43. ...
"Accelerated atherosclerosis and calcification in vein grafts: a study in APOE*3 Leiden transgenic mice". Circulation Research. ... A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association". Circulation. ... Journal of vascular surgery. 51 (2): 429-37. doi:10.1016/j.jvs.2009.09.026. PMID 20036101. Quax, PH; Lamfers, ML; Lardenoye, JH ... and vascular biology. 31 (5): 1033-40. doi:10.1161/ATVBAHA.111.223271. PMID 21330606. Pradhan-Nabzdyk, L; Huang, C; LoGerfo, FW ...
Manev H, Manev R (2006). "5-Lipoxygenase (ALOX5) and FLAP (ALOX5AP) gene polymorphisms as factors in vascular pathology and ... "Mouse PubMed Reference:". Kennedy BP, Diehl RE, Boie Y, Adam M, Dixon RA (May 1991). "Gene characterization and promoter ... "Integrative predictive model of coronary artery calcification in atherosclerosis". Circulation. 120 (24): 2448-54. doi:10.1161/ ... reduces inflammation in the respiratory syncytial virus-infected mouse eye". Clinical and Vaccine Immunology. 16 (11): 1654-9. ...
Studies in mice and rats have found that retinoids, including isotretinoin, bind to dopaminergic receptors in the central ... Other problems include premature epiphyseal closure and calcification of tendons and ligaments.[32] The bones of the spine and ... Vascular *Vasculitis (i.e. Granulomatosis with polyangiitis, allergic vasculitis). Respiratory, thoracic and mediastinal ... suppresses hippocampal cell survival in mice". Annals of the New York Academy of Sciences. 1021 (1): 436-40. Bibcode: ...
Vascular Biology. Aortic Msx2-Wnt Calcification Cascade Is Regulated by TNF-α-Dependent Signals in Diabetic Ldlr−/− Mice. Ziyad ... Figure 1. Diabetogenic diets promote calcification in male Ldlr−/− mice. Mice were fed HFD for 1 (A and B) or 6 (C through F) ... Inactivation of the osteopontin gene enhances vascular calcification of matrix Gla protein-deficient mice: evidence for ... Mice with vascular TNF-α augmented by a transgene (SM22-TNFαTg) driven from the SM22 promoter upregulated aortic Msx2, Wnt3a, ...
To determine whether teriparatide alters vascular calcification, we imaged aortic calcification in mice treated with ... Effects of teriparatide on morphology of aortic calcification in aged hyperlipidemic mice.. Hsu JJ1, Lu J2, Umar S3, Lee JT4, ... Female apolipoprotein E-deficient mice were aged for over 1 yr to induce aortic calcification, treated for 4.5 wk with daily ... NEW & NOTEWORTHY Parathyroid hormone regulates bone mineralization and may also affect vascular calcification, which is an ...
These in vitro data were confirmed and extended by studying an in vivo mouse model of vascular calcification. Mice lacking NPP1 ... Expression of IGF2 is associated with aortic calcification in a mouse model of GACI. The association of IGF2 with vascular ... The vascular biology of calcification. Seminars in Dialysis. 2007;20:103-109. doi: 10.1111/j.1525-139X.2007.00255.x. [PubMed] [ ... In this study, we have carried out in vitro VSMC calcification studies, in conjunction with ex vivo analyses of a mouse model ...
B, Thiamet-G accelerated vascular calcification in diabetic mice. Calcium content was determined in mouse descending aortas and ... Thiamet-G treatment accelerates vascular calcification in diabetic mice. Mice were treated with control, streptozotocin (STZ), ... Administration of Thiamet-G in diabetic mice further enhances vascular O-GlcNAcylation, accelerated vascular calcification and ... D, Increased vascular calcification in diabetic mice. Calcium content was determined in descending aortas from control and STZ- ...
Previously vascular calcification was thought to be a passive process which involved the deposition of calcium and phosphate in ... Previously vascular calcification was thought to be a passive process which involved the deposition of calcium and phosphate in ... However, recent studies have shown that vascular calcification is a highly regulated, cell-mediated process similar to bone ... However, recent studies have shown that vascular calcification is a highly regulated, cell-mediated process similar to bone ...
... mice exhibit exaggerated TNF induction and increased mortality.53 Finally, in the apoE-null mouse, vascular calcification ... Osteoprotegerin inhibits vascular calcification without affecting atherosclerosis in ldlr(−/−) mice. Circulation. 2008; 117: ... atherosclerotic calcification, diabetic medial artery calcification, vascular calcification of end-stage renal disease, and ... Mice. Some degree of vascular inflammation is a frequent concomitant of most forms of arterial calcification.13,14 Sites of ...
Vascular calcification occurs spontaneously in genetically modified mice such as apoE-deficient mice, which were recently shown ... vascular calcification promoting bone loss, (2) bone loss promoting vascular calcification, or (3) a common etiology. The first ... For years, the vascular calcification and osteoporosis phenotypes of the Klotho mouse were attributed to a premature aging ... Osteoprotegerin (OPG) inhibits vascular calcification without affecting atherosclerosis in ldlr(−/−) mice. Circulation. 2008; ...
Klotho-hypomorphic mice (kl/kl) suffer from severe vascular calcification and rapid aging. The calcification is at least in ... In kl/kl mice, ACM reversed tissue calcification despite continued hyperphosphatemia. ACM tripled the life span of kl/kl mice. ... interference with osteoinductive signaling and tissue calcification in kl/kl mice.. KEY MESSAGES: Klotho deficient (kl/kl) mice ... Acetazolamide sensitive tissue calcification and aging of klotho-hypomorphic mice.. Leibrock CB1, Alesutan I1, Voelkl J1, ...
In valves, calcification presents as Calcific Aortic Valve Disease (CAVD), in which the aortic valve becomes stenotic when ... In valves, calcification presents as Calcific Aortic Valve Disease (CAVD), in which the aortic valve becomes stenotic when ... Calcification of either tissue leads to deterioration and, ultimately, failure causing poor quality of life and decreased ... Calcification of either tissue leads to deterioration and, ultimately, failure causing poor quality of life and decreased ...
Downregulation of Msx Signaling Reduces Vascular Calcification and Stiffness in Diabetic Mice. Although arterial calcification ... Downregulation of Msx Signaling Reduces Vascular Calcification and Stiffness in Diabetic Mice ... Targeted reduction of vascular Msx1 and Msx2 mitigates arteriosclerotic calcification and aortic stiffness in LDLR-deficient ... Treated mice also displayed decreased expression of vascular Shh (Sonic hedgehog), which is involved in multipotent mesenchymal ...
Vitamin K2 can inhibit calcification of aortic intima in mice.Dec 31, 2016. ... Panax notoginseng saponins attenuate phenotype switching of vascular smooth muscle cells induced by notch3 silencing.Dec 31, ... Oral treatment with a low dose of THC inhibits atherosclerosis progression in this mouse model.Apr 06, 2005. ... Hawthorn leave flavonoids can slow down the development of atherosclerosis in apoE knockout mice.Feb 22, 2017. ...
Similarly, Sgk1 deficiency blunted vascular calcification in apolipoprotein E-deficient mice after subtotal nephrectomy. ... These observations identified SGK1 as a key regulator of vascular calcification. SGK1 promoted vascular calcification, at least ... Medial vascular calcification, associated with enhanced mortality in chronic kidney disease (CKD), is fostered by osteo-/ ... SGK1 induces vascular smooth muscle cell calcification through NF-κB signaling. ...
Warfarin accelerated vascular calcification and worsened cardiac dysfunction in remnant kidney mice.Dec 31, 2017. ... Diseases : Kidney Failure: Chronic, Lipid Peroxidation, Vascular Calcification. Pharmacological Actions : Anti-Inflammatory ... Diosgenin attenuates vascular calcification in chronic renal failure rats.May 31, 2013. ...
... mice,22 indicating that such a mechanism may be involved in diverse variants of medial vascular calcification, although ... Vascular smooth muscle cell phenotypic plasticity and the regulation of vascular calcification. J Intern Med. 2006;260:192-210. ... A10 cells (A and B) or aortic rings dissected from the TG2−/− mice (C) were cultured in calcification medium and supplemented ... Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature. 1997;386:78-81. ...
2015). ENPP1-Fc prevents mortality and vascular calcifications in rodent model of generalized arterial calcification of infancy ... Calcification levels are also increased in a statistically significant manner in Asj-2J hom mice compared with WT mice in ... Tissue calcification data from Asj-2J mice were used to establish a therapeutic treatment window for a calcification prevention ... These mice present with severe arterial calcification with minor secondary calcification in nonvascular tissues (Fig. 1A). ...
Mice that lack MGP develop to term but die within two months as a result of arterial calcification which leads to blood-vessel ... "A role for the endothelium in vascular calcification". Circ. Res. 113 (5): 495-504. doi:10.1161/CIRCRESAHA.113.301792. PMC ... "Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein". Nature. 386 (6620): 78-81. doi:10.1038 ... The protein acts as an inhibitor of vascular mineralization and plays a role in bone organization. MGP is found in number body ...
Supporting the idea that low fetuin-A causes vascular calcification, we observed in patients with PAD (NGM-PAD and type 2 ... Fetuin-A knockout mice develop severe calcification of various organs (4). In a cross-sectional study, low levels of fetuin-A ... In addition, we support the hypothesis that low fetuin-A might result in vascular calcification. Finally, we are first to ... low fetuin-A has been linked to vascular calcification (6) and flow-limiting aortic stenosis (7). ...
Similarly, Sgk1 deficiency blunted vascular calcification in apolipoprotein E-deficient mice after subtotal nephrectomy. ... These observations identified SGK1 as a key regulator of vascular calcification. SGK1 promoted vascular calcification, at least ... In Ahsp−/− mice, EC α-globin was decreased by 70%. Ahsp−/− and Hba1−/− mice exhibited similar evidence of increased vascular NO ... Medial vascular calcification, associated with enhanced mortality in chronic kidney disease (CKD), is fostered by osteo-/ ...
Conclusions: Inhibition of BMP signaling leads to reduced vascular calcification and improved survival in MGP-/- mice. The ... Aortic calcification was assessed in 28-day-old mice by measuring the uptake of a fluorescent bisphosphonate probe and by ... Aortic calcification was 80% less in MGP-/- mice treated with LDN-193189 or ALK3-Fc compared with vehicle-treated control ... suggest that BMP signal transduction has critical roles in the development of vascular calcification in MGP-deficient mice. ...
Potassium plays a crucial role in staving off arterial calcification, which is associated with kidney disease, cardiovascular ... Potassium plays a crucial role in staving off arterial calcification, which is associated with kidney disease, cardiovascular ... A new study showed that vascular calcification was relieved in animal studies; mice given the highest levels of potassium had ... The scientists noted that vascular smooth muscle cells, or VSMCs, contribute to vascular calcification in atherosclerosis and ...
Clearing out the clutter: senolytic drugs improve vascular health in mice. Reduced calcification of plaques on blood-vessel ... in mice improve age-related vascular conditions - and may possibly reduce cardiovascular disease and death. ... The researchers intermittently gave the mice a cocktail of two senolytic drugs (ones that selectively induce cell death): ... Mayo Clinic researchers extend lifespan by up to 35 percent in mice. February 3, 2016. ...
Figure 3: Mouse calvaria: particle-induced osteolysis. *characterization of dystrophic calcifications. *visualization of bone ... vascular mapping. Equipment. Scanner: Scanco Medical MicroCT 35 (Fig. 4). *Resolution: 1.75-38 microns. In a typical mouse bone ... mouse femur trabecular bone: ,0.5% for mineral density, ,0.7% for trabecular bone volume fraction, relative bone surface, ... Typical scanning time for mouse femurs: 6-10µm resolution ~1.5h (4 femurs can be scanned in parallel). ...
Current Vascular Pharmacology. *Antibacterial Combination of Oleoresin from Copaifera multijuga Hayne and Biogenic Silver ... Susceptibility of Intracellular Coxiella burnetii to Antimicrobial Peptides in Mouse Fibroblast Cells. Protein & Peptide ... Prevention of Bioprosthetic Heart Valve Calcification: Strategies and Outcomes. Author(s): L.P. Bre, R. McCarthy, W. Wang ... Firstly, the calcification process has been studied and factors such as young patient age, use of glutaraldehyde fixative, the ...
Sclerostin is locally produced in aortic valve tissue adjacent to areas of calcification. ... and aortic valve calcifications (AVC) in haemodialysis (HD) patients. We conducted a cross-sectional multi-slice computed ... regarding their association to the presence of calcification. Fifty-four adults without relevant renal disease served as ... Role of calcification inhibitors in the pathogenesis of vascular calcification in chronic kidney disease (CKD). Kidney Int. ...
Teriparatide, a PTH1R agonist that inhibits murine vascular calcification, suppressed vascular BMP2-Msx2-Wnt signaling. ... In diabetic LDLR-/- mice, an ectopic BMP2-Msx2 gene regulatory program is upregulated in association with vascular ... Analyses of CMV-Msx2Tg+ mice confirmed that Msx2 suppresses aortic Dkk1 and upregulates vascular Wnts; moreover, TOPGAL+ (Wnt ... On high-fat diets, CMV-Msx2Tg+ mice exhibited marked cardiovascular calcification involving aortic and coronary tunica media. ...
ArteriesBoneSerumCalciumArteryStiffnessVSMCsArteriosclerosisValvularSmooth musclIncrease in vascular calcificationVSMCBurden of vascular calcificationMechanisms underpinning vascularAtherosclerosis and vascular calcificationInhibitorCardiovascular diseaseApolipoproteinDifferentiationPathogenesisBlood vesselMineralizationMediates vascular calcificationChronicPeripheral vasculaVivoMortalityDeficiencyIdiopathic infantile arterial calcificationDialysisInhibitionPhosphateAtherosclerotic LesionsEnhanced vascular smooth muscPhenotypeMesenchymal stemRenal diseaseMyocardial infarction and strokeExtensive medial calcificationCardiacDietary potassiumOsteoprotegerinAortic arch calcificationEndothelialDiabeticSevereHypertensionApoEKnockoutRegulatesWidespreadInflammation and Calcification
- The process of vascular calcification shares many similarities with that of skeletal mineralisation and involves the deposition of hydroxyapatite crystals in arteries and cardiac valves. (pubmedcentralcanada.ca)
- Increased O-GlcNAcylation in diabetic arteries or in the O-GlcNAcase knockdown vascular smooth muscle cell upregulated expression of the osteogenic transcription factor Runx2 and enhanced activation of AKT. (ahajournals.org)
- Previously vascular calcification was thought to be a passive process which involved the deposition of calcium and phosphate in arteries and cardiac valves. (frontiersin.org)
- 16 - 20 A role for this protein in vascular calcification is suggested by the reported accumulation of either TG2-mediated cross-links or the TG2 protein itself in the calcifying arteries of warfarin-treated rats 21 and MGP −/− mice. (ahajournals.org)
- Generalized arterial calcification of infancy (GACI) is a severe, rare disease characterized by excessive calcification and stenosis of large- and medium-sized arteries. (biologists.org)
- Mice were fed alternate diets containing low, normal or high levels of potassium, and those with the highest levels had substantially more pliable arteries, while those given lower amounts had much harder arteries. (mercola.com)
- The team also assessed the effects of varying potassium levels on cultured vascular smooth muscle cells from mice, as well as on cultured cross sections of mouse arteries. (medicalnewstoday.com)
- Through their analysis of cultured cross sections of mouse arteries and dietary experiments in live mice, the researchers confirmed that low potassium may lead to vascular calcification via calcium signaling, CREB, and autophagy. (medicalnewstoday.com)
- BIRMINGHAM, Ala. - Bananas and avocados -- foods that are rich in potassium -- may help protect against pathogenic vascular calcification, also known as hardening of the arteries. (eurekalert.org)
- Such knowledge of how vascular smooth muscle cells in the arteries regulate vascular calcification emphasizes the need to consider dietary intake of potassium in the prevention of vascular complications of atherosclerosis. (eurekalert.org)
- During the RT surgery, the internal iliac arteries were collected and paraffin-embedded in 40 patients, followed by immunohistochemical staining for sclerostin expression and von Kossa-staining for vascular medial calcification degree. (springer.com)
- In this study, CTRP13 treatment improved endothelium-dependent relaxation in the aortae and mesenteric arteries of both db/db mice and streptozotocin-injected mice. (diabetesjournals.org)
- Divergent effects of matrix metalloproteinases 3, 7, 9, and 12 on atherosclerotic plaque stability in mouse brachiocephalic arteries. (semanticscholar.org)
- Characteristics of intact and ruptured atherosclerotic plaques in brachiocephalic arteries of apolipoprotein E knockout mice. (semanticscholar.org)
- Studies have also shown that even modest amounts of vitamin K2 fight heart disease by controlling calcium-regulating proteins in vascular tissue, which keeps calcium out of the arteries and prevents the formation of dangerous calcified plaques. (lifeextension.com)
- In arterial calcification (arteriosclerosis), pathological deposits form in the arteries and this leads to vascular stenosis. (technologynetworks.com)
- Consistently, elevated autophagy and CREB signaling were demonstrated in the calcified arteries from low potassium diet-fed mice as well as aortic arteries exposed to low potassium ex vivo. (jci.org)
- The overall goal is to test the hypothesis that these novel phenotypes are associated with subclinical atherosclerosis in the coronary and carotid arteries assessed by quantification of coronary calcification (CAC) and B-mode ultrasound (CIMT), in addition to the other subclinical measures available from the MESA cohort. (clinicaltrials.gov)
- Aged arteries are characterized by functional changes of vascular smooth muscle cells (VSMCs) from a contractile and quiescent status to a senescent phenotype. (skincare.nz)
- Arterial calcification is a highly regulated form of tissue mineralization that proceeds via mechanisms resembling membranous and endochondral bone formation. (ahajournals.org)
- Prior work suggests that teriparatide, the bone anabolic treatment for postmenopausal osteoporosis, may inhibit the onset of aortic calcification. (nih.gov)
- NEW & NOTEWORTHY Parathyroid hormone regulates bone mineralization and may also affect vascular calcification, which is an important issue, given that its active fragment, teriparatide, is widely used for the treatment of osteoporosis. (nih.gov)
- However, recent studies have shown that vascular calcification is a highly regulated, cell-mediated process similar to bone formation. (frontiersin.org)
- 4,5 Moreover, as in skeletal development - where unique biology controls matrix mineralization in membranous bone, endochondral bone, dentin, and enamel, 6,7 mechanistic diversity exists in the pathobiology of vascular calcium deposition. (ahajournals.org)
- Previously considered passive and degenerative, vascular calcification is now recognized as a pathobiological process sharing many features with embryonic bone formation. (ahajournals.org)
- Calcifying vascular cells consistently demonstrate signs of osteochondrogenic transdifferentiation, suggesting that similarities exist in molecular regulation between bone development and vascular calcification. (ahajournals.org)
- The protein acts as an inhibitor of vascular mineralization and plays a role in bone organization. (wikipedia.org)
- In a typical mouse bone characterization the resolution used is 6µm (for femur/tibia) or 10µm (for knee). (hss.edu)
- Several of these parameters are also involved in the regulation of bone metabolism and osseous calcification processes. (biomedcentral.com)
- Secondary hyperparathyroidism is a systemic disorder that associates with bone and cardiovascular disease, including arterial calcification. (hindawi.com)
- Core binding factor β of osteoblasts maintains cortical bone mass via stabilization of Runx2 in mice. (upenn.edu)
- We investigated the metabolic phenotype associated with impaired bone metabolism in mice lacking the gene that encodes NPP1 ( Enpp1 −/− mice). (biologists.org)
- Enpp1 −/− mice had increased levels of the insulin-sensitizing bone-derived hormone osteocalcin but unchanged insulin signalling within osteoblasts. (biologists.org)
- Previous research by several labs including Chen's group has shown that calcification of vascular smooth muscle cells resembles the differentiation of bone cells, which leads to the transformation of smooth muscle cells into bone-like cells. (eurekalert.org)
- They found that the low-potassium conditions promoted the expression of several gene markers that are hallmarks of bone cells, but decreased the expression of vascular smooth muscle cell markers, suggesting the transformation of the vascular smooth muscle cells into bone-like cells under low-potassium conditions. (eurekalert.org)
- Methods: Mouse bone marrow cells (BMCs) were stimulated with macrophage colony-stimulating factor into bone marrow macrophages (BMMs). (deepdyve.com)
- Mouse BMCs be a potent stimulator of bone loss in vivo . (deepdyve.com)
- Dysregulation of OPG/TRANCE interactions can lead to juvenile Paget's disease, osteoporosis, bone loss, and vascular calcification. (rndsystems.com)
- In the present study, we explored the role of the interferon-inducible protein p202 in osteoblast differentiation of mouse bone marrow stromal cells (BMSCs). (portlandpress.com)
- Gelsolin is an actin-binding protein that can modulate inflammation, correlated inversely with hemodialysis (HD) mortality and involved in bone calcification homeostasis. (medsci.org)
- Objectives Increasing evidences shown the important role of bone marrow-derived mesenchymal stem cells (BM-MSCs) in wound healing and vascular remodelling in vivo . (bmj.com)
- Furthermore, mouse model and human studies have suggested that bone marrow-derived progenitor cells may contribute to a variety of vascular pathologies including calcification, atherosclerosis and intimal hyperplasia. (bmj.com)
- Therefore, we examined bone growth and remodeling phenotypes in ASHG-deficient mice. (semanticscholar.org)
- Chronic kidney disease (CKD) patients frequently suffer from mineral bone disorder, which causes vascular calcification and, eventually, chronic heart failure. (medicalxpress.com)
- The relationship between bone-related proteins such as osteocalcin and osteoprotegerin and vascular disease is of special interest. (elsevier.es)
- Here, we demonstrate that MSC-CM inhibits beta-glycerophosphate (β-GP)-induced vascular calcification through blockade of the bone morphogenetic protein-2 (BMP2)-Smad1/5/8 signaling pathway. (biomedcentral.com)
- They found that the hormone triggers cells from the blood vessels to produce bone-like deposits - a process called calcification. (newswise.com)
- Dr Vicky MacRae, of the University of Edinburgh's Roslin Institute, said:"Calcification is particularly difficult to treat, as the biological processes behind the disease are similar to those used by our body to make and repair bone. (newswise.com)
- In parallel with our in vitro experiments on human T lymphocytes, we evaluated an in vivo model of bone loss induced in C57BL/6 mice that become hyperlipidemic when treated with a high-fat diet . (natap.org)
- Consistent with our earlier studies , pQCT analysis of femoral bones from high-fat fed mice showed a significant reduction in bone mineral content compared to their chow-fed counterparts (Table 1). (natap.org)
- Senescent VSMCs express bone-related genes, like Runt-related transcription factor 2 (Runx2) , alkaline phosphatase , and osteocalcin that favor their maladaptive switching to an osteoblastic phenotype and eventually, the onset of vascular calcification (VC), a cardiovascular complication characterized by hydroxyapatite crystals deposition and mineralization of the arterial wall. (skincare.nz)
- Methods and Results- HFD promoted obesity, hyperglycemia, and hyperlipidemia, and upregulated serum TNF-α in Ldlr −/− mice. (ahajournals.org)
- We tested established biomarkers as well as serum sclerostin (ELISA) regarding their association to the presence of calcification. (biomedcentral.com)
- Treatment with calcitriol, the active form of vitamin D, reduces parathyroid hormone levels, but may result in elevations in serum calcium and phosphorus, increasing the risk of vascular calcification in dialysis patients. (hindawi.com)
- We investigated whether common CASR gene variants are predictors for aortic and coronary artery calcification or influence risk factors such as serum calcium, phosphate and glucose concentrations in RTRs. (uzh.ch)
- METHODS: Two hundred and eighty four RTRs were investigated for associations between three CASR promoter region single nucleotide polymorphisms (SNPs) (rs115759455, rs7652589, rs1501899), three non-synonymous CASR coding region SNPs (A986S, R990G, Q1011E), and aortic and coronary artery calcium mass scores, cardiovascular outcomes and calcification risk factors that included serum phosphate, calcium, total cholesterol and glucose concentrations. (uzh.ch)
- CONCLUSIONS: Common CASR SNPs may be independent predictors of serum glucose and phosphate concentrations, but are not determinants of vascular calcification or cardiovascular outcomes. (uzh.ch)
- Together with the knowledge that end-stage renal disease patients almost uniformly have both elevated serum phosphate and extensive vascular calcification, this observation raised the possibility that hyperphosphatemia may be a major contributing factor to the calcification in these patients. (ahajournals.org)
- Our recent study suggests that serum CTRP13 is highly associated with vascular calcification in chronic kidney disease, and ectopic CTRP13 infusion dramatically inhibits the osteogenic differentiation of vascular smooth muscle cells and reduces calcium deposition ( 16 ). (diabetesjournals.org)
- In an in vitro model, elevated Ca or P induced human vascular smooth muscle cell (VSMC) calcification independently and synergistically, a process that was potently inhibited by serum. (asnjournals.org)
- These vesicles contain mineralization inhibitors derived from VSMC and serum, and perturbation of the production or function of these inhibitors would lead to accelerated vascular calcification. (asnjournals.org)
- Ldlr −/− mice fed high-fat "Westernized" diets (HFD) accumulate aortic calcium primarily in the tunica media, mediated via osteogenic morphogens and transcriptional programs that induce aortic alkaline phosphatase (ALP). (ahajournals.org)
- In summary, although teriparatide may not affect the calcium mineral content of aortic calcification, it reduces 18 F-NaF uptake in calcified lesions, suggesting the possibility that it may reduce mineral surface area with potential impact on plaque stability. (nih.gov)
- 24 However, because calcium phosphate mineral deposition itself elicits inflammatory responses, 25 including tumor necrosis factor (TNF) production by macrophages, 26,27 a primary role for inflammation in the pathogenesis of clinically relevant vascular calcification was unproven until very recently. (ahajournals.org)
- 15,16 Thus, vascular calcification introduces compliance mismatch that can promote mechanical failure due to stress concentration at the interfaces of calcium deposits with softer plaque components. (ahajournals.org)
- As precipitation of calcium and phosphate is fostered by alkaline pH, extracellular acidosis could counteract tissue calcification. (nih.gov)
- Calcification is a buildup of calcium in your tissues, organs or blood vessels. (mercola.com)
- The cell culture analysis revealed that through a potassium transport channel called the inward rectifier potassium channel, low-potassium conditions led to a rise in intracellular calcium in vascular smooth muscle cells. (medicalnewstoday.com)
- 1 Histopathologically, these calcium deposits are located primarily in the medial layer, unlike atherosclerotic calcification, which is located within the intimal lesions. (ahajournals.org)
- Calcium metabolism of 6 and 17 month-old vitamin D receptor knockout mice: A pilot study. (upenn.edu)
- Too much FGF23 leads to increased take up of calcium by the kidneys, and results in vascular calcification. (vetmeduni.ac.at)
- Yabing Chen, Ph.D. Mechanistically, they found that low-potassium elevated intracellular calcium in the vascular smooth muscle cells, via a potassium transport channel called the inward rectifier potassium channel. (uab.edu)
- Patients with ESRD have a high circulating calcium (Ca) × phosphate (P) product and develop extensive vascular calcification that may contribute to their high cardiovascular morbidity. (asnjournals.org)
- Mechanistically, reduction in the potassium concentration to the lower limit of the physiological range increased intracellular calcium, which activated a cAMP response element-binding protein (CREB) signal that subsequently enhanced autophagy and promoted vascular smooth muscle cell (VSMC) calcification. (jci.org)
- Inhibition of calcium signals and knockdown of either CREB or ATG7, an autophagy regulator, attenuated VSMC calcification induced by low potassium. (jci.org)
- When the mouse cells were modified, by removing the testosterone receptor, so they could no longer respond to testosterone, they produced far less of the calcium deposits. (newswise.com)
- One of the many conditions in which cellular senescence is implicated is vascular calcification , the inappropriate deposition of calcium that stiffens blood vessels and heart tissue. (skincare.nz)
- 1 Lehto identified aortofemoral medial artery calcification as the most significant predictor of lower-extremity amputation. (ahajournals.org)
- Vascular calcification can be categorized into four main types according to location: atherosclerotic intimal calcification, medial artery calcification (Mönckeberg's sclerosis), cardiac valve calcification, and calcific uremic arteriolopathy. (frontiersin.org)
- the molecular "fingerprints" of activated Wnt signaling identified in diabetic medial artery calcification can also be detected in calcifying aortic valves. (ahajournals.org)
- Here, we assessed the potential association of sclerostin with the development of coronary artery (CAC) and aortic valve calcifications (AVC) in haemodialysis (HD) patients. (biomedcentral.com)
- CASR SNPs were not significant determinants for aortic or coronary artery calcification, and were not associated with cardiovascular outcomes or mortality in this RTR cohort. (uzh.ch)
- Vascular calcification is widespread in patients with coronary artery disease, peripheral vascular disease, and diabetes, but by far the most severe and extensive vascular calcification is in those with end-stage renal disease, especially those with the longest exposure to hemodialysis. (ahajournals.org)
- A UAB team led by Yabing Chen, Ph.D., UAB professor of pathology and a Research Career Scientist at the Birmingham VA Medical Center, explored this mechanism of vascular disease three ways: living mice fed diets that varied in potassium, mouse artery cross-sections studied in culture medium with varying concentrations of potassium, and mouse vascular smooth muscle cells grown in culture medium. (eurekalert.org)
- strong course="kwd-title" Keywords: Principal Pulmonary Hypertension Background Pulmonary arterial hypertension (PAH) is certainly a chronic, possibly fatal disease characterised haemodynamically by elevated indicate pulmonary artery pressure 25?mm?Hg, normal pulmonary artery wedge pressure 15?mm?Hg and elevated pulmonary vascular level of resistance (PVR) 3 Timber Units. (exposed-skin-care.net)
- Major reduction of atherosclerosis in fractalkine (CX3CL1)-deficient mice is at the brachiocephalic artery, not the aortic root. (semanticscholar.org)
- VSMC in the normal artery wall constitutively express potent inhibitors of calcification, such as matrix Gla protein (MGP), whose absence results in spontaneous medial calcification ( 8 ). (asnjournals.org)
- The researchers tested this combination method in mice whose carotid artery endothelial cells were injured. (technologynetworks.com)
- Normally, doctors surgically remove vascular deposits from the carotid artery and in some cases place a vascular support (stent) to correct the bottleneck in the crucial blood supply. (technologynetworks.com)
- Previous work undertaken at King's has also shown that Klotho protects the vascular system against changes associated with abnormal ageing, such as the thickening of artery walls (atherosclerosis), which characterises age related disorders such as diabetes, heart disease and hypertension. (medicalxpress.com)
- Aortic calcification, stiffness, and osteo-/chondrogenic transdifferentiation in mice following cholecalciferol overload were strongly reduced by genetic knockout or pharmacological inhibition of Sgk1 by EMD638683. (jci.org)
- The scientists noted that vascular smooth muscle cells, or VSMCs, contribute to vascular calcification in atherosclerosis and that "Arterial stiffness has become an independent predictor of cardiovascular morbidity and mortality, representing an important health problem for the nation as a whole. (mercola.com)
- Increased pulse pressure, left ventricular hypertrophy, and arrhythmias, resulting from arterial stiffness, have been suggested as potential effects of arterial calcification that may lead to cardiovascular disease and death. (hindawi.com)
- The researchers found that mice fed a low-potassium diet showed an increase in vascular calcification and greater arterial stiffness, while mice fed a high-potassium diet showed a significant reduction in both conditions. (medicalnewstoday.com)
- University of Alabama at Birmingham researchers have shown, for the first time, that reduced dietary potassium promotes elevated aortic stiffness in a mouse model, as compared with normal-potassium-fed mice. (eurekalert.org)
- The UAB researchers also found that increased dietary potassium levels lessened vascular calcification and aortic stiffness. (eurekalert.org)
- It also provides new targets for potential therapies to prevent or treat atherosclerotic vascular calcification and arterial stiffness. (eurekalert.org)
- Also, the low-potassium mice had increased stiffness of their aortas, and high-potassium mice had decreased stiffness, as indicated by the arterial stiffness indicator called pulse wave velocity, which is measured by echocardiography in live animals. (eurekalert.org)
- Several approaches can be considered to reduce vascular stiffness and improve vascular function in patients with CKD. (asnjournals.org)
- Arterial stiffness is a vascular biomarker 4 that is increased in patients with CKD, 5 - 8 even in those with a mildly impaired renal function, 5 and is associated with an independent increase in CV risk. (asnjournals.org)
- 7 The increase of arterial stiffness in CKD is mostly caused by reduced renal excretion of vascular toxins, maladaptive metabolic and hormonal processes, and as a result, premature vascular aging. (asnjournals.org)
- Using the ApoE-deficient mouse model, we demonstrated for the first time to our knowledge that reduced dietary potassium (0.3%) promoted atherosclerotic vascular calcification and increased aortic stiffness, compared with normal (0.7%) potassium-fed mice. (jci.org)
- In contrast, increased dietary potassium (2.1%) attenuated vascular calcification and aortic stiffness. (jci.org)
- These studies established a potentially novel causative role of dietary potassium intake in regulating atherosclerotic vascular calcification and stiffness, and uncovered mechanisms that offer opportunities to develop therapeutic strategies to control vascular disease. (jci.org)
- Targeted reduction of vascular Msx1 and Msx2 mitigates arteriosclerotic calcification and aortic stiffness in LDLR-deficient mice fed diabetogenic diets Diabetes. (usc.edu)
- 9000 genes during the calcification of murine vascular smooth muscle cells (VSMCs), of which the most significantly, differentially expressed gene was Igf2 . (pubmedcentralcanada.ca)
- Following the validation of increased IGF2 expression by RT-qPCR and immunoblotting in calcifying murine VSMCs, IGF2 expression was further demonstrated in the calcified aorta of the Enpp1 −/− mouse model of medial aortic calcification. (pubmedcentralcanada.ca)
- Medial vascular calcification, associated with enhanced mortality in chronic kidney disease (CKD), is fostered by osteo-/chondrogenic transdifferentiation of vascular smooth muscle cells (VSMCs). (jci.org)
- Genetic deficiency, silencing, and pharmacological inhibition of SGK1 dissipated phosphate-induced calcification and osteo-/chondrogenic transdifferentiation of VSMCs. (jci.org)
- Objective- Accumulating experimental evidence implicates β-catenin signaling and enzyme transglutaminase 2 (TG2) in the progression of vascular calcification, and our previous studies have shown that TG2 can activate β-catenin signaling in vascular smooth muscle cells (VSMCs). (ahajournals.org)
- Methods and Results- Warfarin-induced calcification in rat A10 VSMCs is associated with the activation of β-catenin signaling and is independent of oxidative stress. (ahajournals.org)
- The canonical β-catenin inhibitor Dkk1, but not the Wnt antagonist Wif-1, prevents warfarin-induced activation of β-catenin, calcification, and osteogenic transdifferentiation in VSMCs. (ahajournals.org)
- Conclusion- TG2 is a critical mediator of warfarin-induced vascular calcification that acts through the activation of β-catenin signaling in VSMCs. (ahajournals.org)
- This pharmacodynamic effect of warfarin is based on its chemical similarity to vitamin K. 10 In addition, in a manner similar to vitamin K2, warfarin can directly activate the transcription factor pregnane X receptor, 10 thus affecting the expression of osteogenic genes that are upregulated during the osteoblast-like transformation of calcifying vascular smooth muscle cells (VSMCs). (ahajournals.org)
- 22 Moreover, experiments using cultured VSMCs and aortic rings have shown that TG2 enhances calcification in elevated inorganic phosphate (Pi), 23 , 24 whereas genetic ablation of TG2 prevents this, 24 identifying this enzyme as a key regulator of Pi-induced calcification in vitro, although no mechanistic insights have been specified. (ahajournals.org)
- 6 Further, VSMCs were found to produce "extracellular matrix proteins" that actually caused the arterial calcification process to happen faster. (mercola.com)
- MGP deficiency is associated with medial calcification of the arterial wall, in a process that involves both osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs) and mesenchymal transition of endothelial cells (EndMT). (harvard.edu)
- Calcification of isolated VSMCs was also inhibited by LDN-193189. (harvard.edu)
- Osteoblastic differentiation of vascular smooth muscle cells (VSMCs) plays an important role in arterial calcification and is characterized by cellular necrosis, inflammation, and lipoprotein and phospholipid complexes, especially in atherosclerotic calcification. (biomedcentral.com)
- Hence, the vascular age-associated miR-34a promotes VSMCs SASP activation and contributes to arterial inflammation and dysfunctions such as VC. (skincare.nz)
- Vascular Discovery: From Genes to Medicine is sponsored by the Council on Arteriosclerosis, Thrombosis and Vascular Biology and the Peripheral Vascular Disease Council , in cooperation with the Council on Genomic and Precision Medicine , and the Society for Vascular Surgery. (heart.org)
- The primary goal of this virtual event is to provide a forum for the exchange of information about new and emerging scientific research in lipids and lipoproteins, arteriosclerosis, thrombosis, vascular biology, genomics and peripheral vascular disease. (heart.org)
- Additionally, it is believed that they play a role in wound healing processes, but also in pathological events, for instance those that occur during vascular calcification (arteriosclerosis). (eurekalert.org)
- Aortic valve calcification is also believed to involve the differentiation of valvular interstitial cells (VICs) into an osteoblast-like phenotype ( Monzack & Masters 2011 ). (pubmedcentralcanada.ca)
- Further, there are similarities between vascular smooth muscle cells and valvular interstitial cells in terms of their roles in ECM overproduction. (frontiersin.org)
- This review summarizes valvular and vascular tissue in terms of their basic anatomy, their cellular and ECM components and mechanical forces. (frontiersin.org)
- In fact, while these conditions are seemingly similar, treatments that help reduce calcification in vasculature have been shown to have no effect on valvular calcification. (frontiersin.org)
- As such, most research has looked at vascular and valvular calcification separately although they share similar risk factors and may have overarching parallels. (frontiersin.org)
- 23 β-Catenin signaling is a key pathway in osteogenesis 25 that has been implicated in diabetes-associated medial calcification 26 and in valvular calcification. (ahajournals.org)
- The aim of the present study was to assess whether CVC in haemodialysis patients is associated with levels of circulating sclerostin and whether valvular calcification goes along with local sclerostin production. (biomedcentral.com)
- Here, we review efforts taken in understanding the valvular response to its mechanical milieu and key insights gained from in vitro and ex vivo whole-tissue studies in the mechanobiology of aortic valve remodeling, inflammation, and calcification. (hindawi.com)
- Increased O-GlcNAcylation, either by Thiamet-G or O-GlcNAcase knockdown, promoted calcification of primary mouse vascular smooth muscle cells. (ahajournals.org)
- To investigate possible mechanisms, different atherogenic cell types (e.g., macrophages, dendritic cells, HUVECs, vascular smooth muscle cells) were stimulated with IL-17A in addition to TNF-α, IFN-γ, or LPS to induce cellular activation or apoptosis in vitro. (jimmunol.org)
- In addition, we investigated possible mechanisms of IL-17A on atherogenic cells (vascular smooth muscle cells (VSMC), monocytes/macrophages, HUVECs, DCs, and CD4 + T cells) in vitro. (jimmunol.org)
- By inhibiting autophagy, the researchers found that they were able to prevent calcification in vascular smooth muscle cells, indicating that autophagy plays a significant role in the calcification process. (medicalnewstoday.com)
- In cell culture, low potassium levels in the culture media markedly enhanced calcification of vascular smooth muscle cells. (eurekalert.org)
- So the UAB researchers tested the effect of growing vascular smooth muscle cells in low-potassium cell culture. (eurekalert.org)
- Zhu D, Mackenzie NC, Millan JL, Farquharson C, MacRae VE (2011) The appearance and modulation of osteocyte marker expression during calcification of vascular smooth muscle cells. (springer.com)
- The objective of this work was to examine the ability of 17β-estradiol (E2) to stimulate calcification of vascular smooth muscle cells (VSMC) in vivo, using aged apolipoprotein E-null mice with advanced atherosclerotic lesions, and subsequently to explore underlying mechanisms in vitro. (ovid.com)
- miR-34a and IL6 levels increased and positively correlated in aortas of 21 months-old male C57BL/6J mice and in human aortic smooth muscle cells (HASMCs) isolated from donors of different age and undergone senescence. (skincare.nz)
- Using low, normal or high levels of dietary potassium -- 0.3 percent, 0.7 percent and 2.1 percent weight/weight, respectively, the UAB team found that the mice fed a low-potassium diet had a significant increase in vascular calcification. (eurekalert.org)
- These results potentially indicate that IGF2 may mediate VSMC calcification via the stimulation of Erk1/2 and Akt signalling. (pubmedcentralcanada.ca)
- Calcification was initiated by release from living VSMC of membrane-bound matrix vesicles (MV) and also by apoptotic bodies from dying cells. (asnjournals.org)
- The potent mineralization inhibitor matrix Gla protein was found to be present in MV, and pretreatment of VSMC with warfarin markedly enhanced vesicle calcification. (asnjournals.org)
- Calcification is initiated in nodules by release of apoptotic bodies (AB) and matrix vesicle (MV)-like structures from VSMC that act as a nidus for BCP nucleation ( 10 ). (asnjournals.org)
- VSMC-derived MV have been associated with calcification in vivo , but their composition and function are poorly understood ( 12 ). (asnjournals.org)
- VSMC calcification was induced by β-GP followed by treatment with MSC-CM. Mineral deposition was assessed by Alizarin Red S staining. (biomedcentral.com)
- Further study demonstrated that human recombinant BMP-2 overcame the suppression of VSMC calcification by MSC-CM. (biomedcentral.com)
- We have demonstrated that E2 can drive calcification in advanced atherosclerotic lesions by promoting the differentiation of VSMC to osteoblast-like cells, a process which is augmented by inhibition of estrogen receptor alpha or ERβ activity. (ovid.com)
- 2,4,11 We end by summarizing the importance of considering these disease stage- and context-specific contributions arterial mineralization when crafting therapeutic strategies to address the disease burden of vascular calcification that increasingly afflicts our patients. (ahajournals.org)
- With increasing age and dysmetabolic conditions in our population, the clinical burden of vascular calcification will continue to increase. (ahajournals.org)
- Inhibition of SGK1 may, thus, reduce the burden of vascular calcification in CKD. (jci.org)
- In this review, we will describe the mechanisms underpinning vascular calcification and discuss the risk factors, clinical consequences, and potential therapeutic targets for this pathological process. (frontiersin.org)
- Matrix metalloproteinases (MMPs) have been implicated in atherosclerosis and vascular calcification. (bioportfolio.com)
- C1q/tumor necrosis factor-related protein 13 (CTRP13) is a secreted adipokine that can ameliorate atherosclerosis and vascular calcification. (diabetesjournals.org)
- Elevation of O-GlcNAcylation by administration of Thiamet-G, a potent inhibitor for O-GlcNAcase that removes O-GlcNAcylation, further accelerated vascular calcification and worsened aortic compliance of diabetic mice in vivo. (ahajournals.org)
- The main function of ENPP1 is to hydrolyze extracellular adenosine triphosphate (ATP) into adenosine monophosphate (AMP) and pyrophosphate (PP i ), a potent physiological inhibitor of hydroxyapatite formation and vascular calcification. (biologists.org)
- OBJECTIVE Low levels of fetuin-A, a systemic calcification inhibitor, are linked to mortality in patients on dialysis. (diabetesjournals.org)
- Fetuin-A, also known as α2-Schmid Heremans glycoprotein (ASHG), is a potent systemic calcification inhibitor ( 4 ). (diabetesjournals.org)
- 8 Other genetic abnormalities also feature vascular calcification as a phenotype, including deficiencies of osteoprotegerin, fibrillin, and NPP1, the enzyme that produces pyrophosphate, an alkaline phosphatase inhibitor. (ahajournals.org)
- Fetuin-A is therefore regarded as a potent inhibitor of systemic calcification. (wikipedia.org)
- Fetuin-A was originally discovered to be an inhibitor of vascular calcification in early 1990s. (wikipedia.org)
- The animal study found it reduces vascular calcification, one of the complications of kidney disease and cardiovascular disease. (mercola.com)
- Mayo Clinic researchers have demonstrated the first study in which repeated treatments to remove senescent cells (cells that stop dividing due to age or stress) in mice improve age-related vascular conditions - and may possibly reduce cardiovascular disease and death. (kurzweilai.net)
- In the last 10 years, several studies pointed out that vascular calcification is a major cause of cardiovascular disease in the dialysis population. (hindawi.com)
- BACKGROUND: Cardiovascular disease is the major cause of death in renal transplant recipients (RTRs) and linked to arterial calcification. (uzh.ch)
- The animal work was carried out in the atherosclerosis-prone mouse model, the apoliprotein E-deficient mice, a standard model that are prone to cardiovascular disease when fed a high-fat diet. (eurekalert.org)
- The inhibition of FGF23 or its pathway could be a possibility to bring cardiovascular disease and vascular calcification under control. (vetmeduni.ac.at)
- Arterial calcification is associated with cardiovascular disease as a complication of advanced atherosclerosis and is a significant contributor to cardiovascular morbidity and mortality. (biomedcentral.com)
- Female apolipoprotein E-deficient mice were aged for over 1 yr to induce aortic calcification, treated for 4.5 wk with daily injections of control vehicle (PBS), 40 µg/kg teriparatide (PTH40), or 400 µg/kg teriparatide (PTH400), and assayed for aortic calcification by microcomputed tomography (microCT) before and after treatment. (nih.gov)
- In a followup cohort, aged female apolipoprotein E-deficient mice were treated with PBS or PTH400 and assayed for aortic calcification by serial microCT and micropositron emission tomography. (nih.gov)
- Similarly, Sgk1 deficiency blunted vascular calcification in apolipoprotein E-deficient mice after subtotal nephrectomy. (jci.org)
- Aortic root sections from 8-wk-old apolipoprotein E-deficient mice fed a standard chow diet were examined after 12 wk for lesion area, plaque composition, cellular infiltration, cytokine expression, and apoptosis. (jimmunol.org)
- Functional blockade of IL-17A reduces atherosclerotic lesion development and decreases plaque vulnerability, cellular infiltration, and tissue activation in apolipoprotein E-deficient mice. (jimmunol.org)
- To test the hypothesis that IL-17A accelerates atherogenesis, we blocked IL-17A with an anti-IL-17A Ab (mAb) in apolipoprotein E-deficient (apoE −/− ) mice, a well established mouse model for atherosclerosis ( 12 ). (jimmunol.org)
- The mice used were deficient in a protein called apolipoprotein E, which makes rodents more susceptible to atherosclerosis in response to a high-fat diet. (medicalnewstoday.com)
- Background We performed in vivo micro-computed tomography (micro-CT) imaging using a novel carbon nanotube (CNT)-based x-ray source to detect calcification in the aortic arch of apolipoprotein E (apoE)-null mice. (ahajournals.org)
- 4 We previously demonstrated that apolipoprotein E (apoE)-null mice with a 129S6/SvEvTac strain background (129-apoE KO) develop more atherosclerotic plaques in the aortic arch than those with a C57BL/6J background (B6-apoE KO). (ahajournals.org)
- The lamina adventitia is the major site of immune cell accumulation in standard chow-fed apolipoprotein E-deficient mice. (semanticscholar.org)
- Inhibition of sphingomyelin synthesis reduces atherogenesis in apolipoprotein E-knockout mice. (semanticscholar.org)
- Silastic E2 capsules were implanted into male and female apolipoprotein E-null mice aged 34 weeks. (ovid.com)
- Preusch MR, Bea F, Yang SH, Kreuzer J, Isermann B, Pedal I, Rosenfeld ME, Katus HA, Blessing E. Long-term administration of 3-deazaadenosine does not alter progression of advanced atherosclerotic lesions in apolipoprotein E-deficient mice. (uni-heidelberg.de)
- Anti-atherosclerotic properties of telmisartan in advanced atherosclerotic lesions in apolipoprotein E deficient mice. (uni-heidelberg.de)
- Dabigatran etexilate retards the initiation and progression of atherosclerotic lesions and inhibits the expression of oncostatin M in apolipoprotein E-Deficient mice. (uni-heidelberg.de)
- Previously considered a passive, unregulated, and degenerative process occurring in the arterial media, vascular calcification has now been demonstrated to be a highly regulated process of osteochondrogenic differentiation of vascular cells. (mercola.com)
- He has also studied the biology of differentiation and phenotypic switching in vascular SMCs, first identifying differentially regulated genes associated with SMC lineage determination, and then focusing on the epigenetic regulation of SMC differentiation state. (stanford.edu)
- In view of the capacity of differentiation into osteoblast from BM-MSCs, we investigated whether BM-MSCs was involved in the process of angiosteosis in atherosclerosis when exposed to vascular injure and hyperlipemia. (bmj.com)
- It is widely accepted that endothelial cell (EC) dysfunction, inflammatory cell recruitment, and vascular smooth muscle cell (SMC) de-differentiation contribute to atherogenesis [ 3 , 4 , 7 ]. (thno.org)
- In this brief review and perspective, we recount recent data that emphasize inflammation and oxidative stress signaling as key contributors to the pathogenesis of vascular mineral deposition. (ahajournals.org)
- The first robust evidence for the primary contributions of inflammatory cytokine signaling to pathogenesis of vascular calcification arose from the generation and evaluation of the osteoprotegerin (OPG) −/− mouse. (ahajournals.org)
- We are also investigating the biomolecular pathways implicated in the pathogenesis of isolated slow-flow vascular malformations with focus on local, sustained delivery of inhibitory agents. (yale.edu)
- The pathogenesis of vascular complications is multifactorial and is probably the combination of direct glucose-mediated endothelial damage, oxidative stress, production of sorbitol, and advanced glycation end-products (AGEs) . (termedia.pl)
- Mice that lack MGP develop to term but die within two months as a result of arterial calcification which leads to blood-vessel rupture. (wikipedia.org)
- A major focus of our laboratory is to understand the healing and function of blood vessels and synthetic blood vessel substitutes and patches that are used in vascular reconstruction. (yale.edu)
- Scientists at the University of Edinburgh examined the effects of testosterone on blood vessel tissue from mice. (newswise.com)
- Understanding the contribution of vascular cells to blood vessel remodeling is critical for the development of new therapeutic approaches to cure cardiovascular diseases (CVDs) and regenerate blood vessels. (thno.org)
- In the past two decades, several types of vascular stem cells (VSCs), in addition to circulating progenitors, have been identified and characterized, with evidence that they are not only involved, but also play pivotal roles in blood vessel remodeling and disease development. (thno.org)
- By understanding better the molecular pathways and genetic circuitry responsible for the pathological mineralization process novel drug targets may be identified and exploited to combat and reduce the detrimental effects of vascular calcification on human health. (frontiersin.org)
- Although both heart valves and vasculature exhibit calcification and share some of the underlying processes leading toward mineralization, few significant correlations between the two have been made. (frontiersin.org)
- In this study, the efficacy of a recombinant human ENPP1 protein therapeutic (rhENPP1) was tested in Enpp1 asj-2J homozygous mice ( Asj-2J or Asj-2J hom), a model previously described to show extensive mineralization in the arterial vasculature, similar to GACI patients. (biologists.org)
- Firstly, the calcification process has been studied and factors such as young patient age, use of glutaraldehyde fixative, the presence of phospholipids along with cell debris in the valve tissue and mechanical stress have been identified to influence tissue mineralization. (eurekaselect.com)
- These investigators went on to show that phosphate supplements also accelerate mineralization in vascular cells and implicated sodium-dependent phosphate transport. (ahajournals.org)
- 2 In this issue of Circulation Research , these investigators 3 now provide compelling evidence that a specific phosphate transporter is essential for in vitro vascular calcification and, possibly, the severe mineralization of the vascular tree in end-stage renal disease patients. (ahajournals.org)
- Feeding a mineral-rich diet to fetuin-A-deficient mice resulted in widespread calcification (ectopic mineralization) of lung, heart, and kidneys in these mice. (wikipedia.org)
- Methods In the Treatment of Ectopic Mineralization in Pseudoxanthoma Elasticum trial, adults with PXE and leg arterial calcifications (n = 74) were randomly assigned to etidronate or placebo (cyclical 20 mg/kg for 2 weeks every 12 weeks). (onlinejacc.org)
- Sundberg, John 2016-04-28 00:00:00 Dystrophic cardiac calcinosis (DCC), also called epicardial and myocardial fibrosis and mineralization, has been detected in mice of a number of laboratory inbred strains, most commonly C3H/HeJ and DBA/2J. (deepdyve.com)
- Calbindin-D 9K mediates vascular calcification from high dose Vitamin D injection via blocking BMP signaling pathway. (upenn.edu)
- Medial arterial calcification is common in patients with chronic kidney disease and diabetes mellitus. (ahajournals.org)
- In the chronic remodeling phase after MI, endothelial- and macrophage-derived Angpt2 continuously promoted abnormal vascular remodeling and proinflammatory macrophage polarization through integrin α5β1 signaling, worsening cardiac hypoxia and inflammation. (jci.org)
- In fact, a 2009 study is even titled "Vascular calcification: the killer of patients with chronic kidney disease. (mercola.com)
- Enpp1 −/− mice exhibited mildly improved glucose homeostasis on a normal diet but showed a pronounced resistance to obesity and insulin resistance in response to chronic high-fat feeding. (biologists.org)
- Their effect on the arterial wall, direct or mediated by chronic inflammation and oxidative stress, results in arterial stiffening and decreased vascular compliance. (asnjournals.org)
- Using mice, investigators found that soft-tissue calcification, a common and serious side effect of chronic kidney disease (CKD), improves when Klotho hormone levels are restored. (healthcanal.com)
- Mice with chronic kidney disease exhibit low levels of Klotho in their kidneys, blood and urine, indicating that CKD is a state of systemic Klotho deficiency, Dr. Moe said. (healthcanal.com)
- Whereas medial calcification is a hallmark of diabetes and chronic kidney disease, arterial calcification is clearly associated with the mortality risk in individuals with atherosclerosis and diabetes. (biomedcentral.com)
- Macrovascular complications include coronary heart disease (CHD), which may result in myocardial infarction, cerebrovascular disease, leading to strokes, and peripheral vascular disease [5- (termedia.pl)
- Moreover, warfarin-induced calcification is significantly reduced on the background of attenuated TG2 both in vitro and in vivo. (ahajournals.org)
- Though not all the factors listed have been definitely linked to vascular calcification, some evidence has been reported at the level of in vitro, in vivo, or clinical studies, for each. (ahajournals.org)
- Koos R, Brandenburg V, Mahnken AH, Schneider R, Dohmen G, Autschbach R, Marx N, Kramann R (2013) Sclerostin as a potential novel biomarker for aortic valve calcification: an in-vivo and ex-vivo study. (springer.com)
- CTRP13 supplement also rescued the impaired endothelium-dependent relaxation ex vivo in the db/db mouse aortae and in high glucose (HG)-treated mouse aortae. (diabetesjournals.org)
- We also study remodeling of tissue engineered vascular grafts using both in vivo and in vitro models. (yale.edu)
- Here, we aimed to invhestigate vascular osteoprotegerin expression and its effects on pulmonary arterial smooth muscle cell proliferation in vitro and in vivo, as well as examine the signal transduction pathways mediating its activity. (ahajournals.org)
- Importantly, T lymphocytes from these mice, tested immediately ex vivo, in the absence of any stimulation, expressed RANKL mRNA that was significantly greater than that of T lymphocytes from the chow-fed mice. (natap.org)
- Vascular calcification is a serious cardiovascular complication that contributes to the increased morbidity and mortality of patients with diabetes mellitus. (ahajournals.org)
- 1 This vascular calcification reduces aortic and arterial elastance, which impairs cardiovascular hemodynamics, resulting in substantial morbidity and mortality 2-4 in the form of hypertension, aortic stenosis, cardiac hypertrophy, myocardial and lower-limb ischemia, congestive heart failure, and compromised structural integrity. (ahajournals.org)
- GACI is associated with a high mortality rate, with death typically occurring from vascular occlusion and additional cardiovascular complications. (biologists.org)
- Patients on HD are at increased risk for fracture (including hip fracture) and vascular calcification, which results in significant morbidity (including hospitalization) and mortality [ 3 ]. (hindawi.com)
- Vascular calcification (VC) is a key process associated with cardiovascular mortality in dialysis patients. (medsci.org)
- Vascular calcification (VC) is increasingly recognized as a key process contributing to the high cardiovascular mortality in dialysis patients [ 2 - 4 ]. (medsci.org)
- Our previous study on 712 prevalent hemodialysis (HD) patients showed a strong correlation between aortic arch calcification (AAC) and 10-year mortality [ 5 ]. (medsci.org)
- Experiments involving knockout mice deficient in the MPO gene (MPO -/- ) revealed several dramatic effects of MPO removal relative to wild-type (WT) controls: By enhancing mitochondrial activity in brown adipose tissue (BAT) and raising body temperature, MPO deficiency reduced the HFD-related tendency toward obesity. (diabetesjournals.org)
- Matrix metalloproteinase-10 deficiency delays atherosclerosis progression and plaque calcification. (bioportfolio.com)
- and the third, that Klotho deficiency contributes to vascular calcification and Klotho replacement ameliorates CKD via multiple mechanisms. (healthcanal.com)
- Fetuin-A deficiency dramatically increased the calcification proneness of these mice in that all mice sponteneously calcified throughout their body even without a mineral-rich diet or surgical tissue trauma. (wikipedia.org)
- Potassium deficiency appears to cause vascular calcification in mice, while increased dietary potassium may reduce heart disease and reduce risk of death, according to a recent study published in JCI Insight. (nutraingredients.com)
- The link between aortic rigidity and heart failure is most evident in the hypertensive cardiomyopathy observed in patients with idiopathic infantile arterial calcification and in animal models with aortic banding. (ahajournals.org)
- Recently, Terkeltaub and colleagues have shown endochondral calcification in aortas of mice deficient in NPP1, 10 the human disease correlate of which is a fatal congenital disorder, idiopathic infantile arterial calcification. (ahajournals.org)
- Therefore, we hypothesized that sclerostin is also linked to vascular calcification in dialysis patients. (biomedcentral.com)
- Inhibition of canonical β-catenin pathway or TG2 activity prevents warfarin-regulated calcification, identifying the TG2/β-catenin axis as a novel therapeutic target in vascular calcification. (ahajournals.org)
- Warfarin inactivates several regulators of tissue calcification, including matrix Gla protein (MGP) 8 and growth arrest-specific gene 6 protein, 9 through inhibition of their vitamin K-dependent carboxylation. (ahajournals.org)
- This association persisted in multivariate regression, which is in line with the calcification inhibition in coronary heart or renal disease. (diabetesjournals.org)
- Conclusions: Inhibition of BMP signaling leads to reduced vascular calcification and improved survival in MGP-/- mice. (harvard.edu)
- The calcification is at least in part caused by excessive 1,25(OH)2D3, Ca(2+), and phosphate concentrations in blood, which trigger osteogenic signaling including upregulation of alkaline phosphatase (Alpl). (nih.gov)
- 05-05-2014 - Why phosphate rich foods can increase blood pressure and promote vascular calcifications has been discovered by scientists at the Vetmeduni Vienna. (vetmeduni.ac.at)
- Most importantly, Klotho also appears to inhibit vascular smooth-muscle phosphate uptake and calcification, a complication of CKD that can significantly increase risk of death. (healthcanal.com)
- Calcification is a common finding in human atherosclerotic lesions, and arterial calcification is generally classified into calcification within an atherosclerotic plaque. (biomedcentral.com)
- Advanced atherosclerotic lesions were present in all mice at the end of 8 weeks. (ovid.com)
- O-GlcNAcylation of AKT at two new sites, T430 and T479, promoted AKT phosphorylation, which in turn enhanced vascular smooth muscle cell calcification. (ahajournals.org)
- This lack of genotype-phenotype correlation prompted us to directly test the possible effects of genetic background or modifier genes on PTEN-controlled tumorigenesis using genetically engineered mouse models. (aacrjournals.org)
- Most recently he has examined the role of microRNAs in the regulation of SMC phenotype, and studied the biology of aortic aneurysm development in mouse models. (stanford.edu)
- Here, we report susceptibility to cardiac fibrosis, a sub-phenotype of DCC, at 12 and 20 months of age and close to natural death in a survey of 28 inbred mouse strains. (deepdyve.com)
- Transplantation of betatrophin-expressing adipose-derived mesenchymal stem cells induces ß-cell proliferation in diabetic mice. (abcam.com)
- Vascular calcification (VC) is known to be prevalent in patients with end-stage renal disease (ESRD). (springer.com)
- Vascular calcification has severe clinical consequences and is considered an accurate predictor of future adverse cardiovascular events, including myocardial infarction and stroke. (frontiersin.org)
- Vascular calcification is associated with increased risk of myocardial infarction and stroke. (ovid.com)
- Warfarin treatment correlates with cardiovascular calcification in human patients 1 - 4 and causes rapid and extensive medial calcification in animal models. (ahajournals.org)
- Vascular calcification involves the deposition of hydroxyapatite crystals in blood vessels, valves and cardiac muscle. (pubmedcentralcanada.ca)
- There is currently no effective treatment available, but bisphosphonates - nonhydrolyzable PP i analogs - are being used off-label to reduce arterial calcification, although this has no reported impact on the hypertension and cardiac dysfunction features of GACI. (biologists.org)
- This study suggests that ENPP1 enzyme replacement therapy could be a more effective GACI therapeutic than bisphosphonates, treating not just the vascular calcification, but also the hypertension that eventually leads to cardiac failure in GACI patients. (biologists.org)
- Cardiac Fibroblasts Adopt Osteogenic Fates and Can Be Targeted to Attenuate Pathological Heart Calcification. (abcam.com)
- Although it remains controversial whether vascular calcification promotes plaque destabilization, it is clear that arterial rigidity contributes to hypertension, cardiac hypertrophy, and heart failure, in part because of increased aortic impedance, as seen in experimental models that use aortic banding to produce heart failure. (ahajournals.org)
- Cardiac and respiratory gated images were acquired in each mouse under anesthesia. (ahajournals.org)
- However, the limited temporal resolution and high-frequency, nonperiodic cardiac and respiratory motion of mice make it difficult to image moving structures. (ahajournals.org)
- Eight strains showed cardiac fibrosis with highest frequency and severity in the moribund mice. (deepdyve.com)
- Mouse model research unraveled the molecular mechanism underlying the effects of low or high dietary potassium. (nutraceuticalsworld.com)
- Researchers have found that mice with low dietary potassium are more likely to experience vascular calcification, which is characteristic of atherosclerosis . (medicalnewstoday.com)
- Increasing dietary potassium , however, was found to reduce vascular calcification in the rodents, suggesting that a diet rich in potassium could help to prevent heart disease. (medicalnewstoday.com)
- Working from living mice down to molecular events in cells in culture, the UAB researchers determined a causative link between reduced dietary potassium and vascular calcification in atherosclerosis, as well as uncovered the underlying pathogenic mechanisms. (eurekalert.org)
- The different levels of dietary potassium were mirrored by different blood levels of potassium in the three groups of mice. (eurekalert.org)
- Osteoprotegerin inactivation accelerates advanced atherosclerotic lesion progression and calcification in older ApoE-/- mice. (semanticscholar.org)
- Moreover, osteoprotegerin disruption attenuated hypoxia plus SU5416-induced PAH progression by reducing pulmonary vascular remodeling, whereas lentiviral osteoprotegerin reconstitution exacerbated PAH by increasing pulmonary arterial smooth muscle cell proliferation. (ahajournals.org)
- Aortic arch calcification has been shown to be independently associated with an increased risk of cardiovascular diseases. (ahajournals.org)
- 5 - 7 In this study, we explored the feasibility of detecting calcification in aortic arch plaques using CNT-based micro-CT and compared aortic arch calcification volume between the 2 strains of apoE-knockout (KO) mice. (ahajournals.org)
- In this report, we aim to characterize progression in aortic arch calcification (AAC) and investigate its association with gelsolin. (medsci.org)
- Aortic arch calcification, gelsolin, hemodialysis. (medsci.org)
- Both diseases show that the endothelial layer and its regulation of nitric oxide is crucial to calcification progression. (frontiersin.org)
- Angpt2 was highly expressed in endothelial cells at the infarct border zone after myocardial infarction (MI) or ischemia/reperfusion injury in mice. (jci.org)
- In the acute phase of MI, endothelial-derived Angpt2 antagonized Angpt1/Tie2 signaling, which was greatly involved in pericyte detachment, vascular leakage, increased adhesion molecular expression, degradation of the glycocalyx and extracellular matrix, and enhanced neutrophil infiltration and hypoxia in the infarct border area. (jci.org)
- Arteriolar endothelial cell-expressed (EC-expressed) α-globin binds endothelial NOS (eNOS) and degrades its enzymatic product, NO, via dioxygenation, thereby lessening the vasodilatory effects of NO on nearby vascular smooth muscle. (jci.org)
- Additionally, CTRP13 treatment reduced reactive oxygen species overproduction and improved nitric oxide (NO) production and endothelial NO synthase (eNOS) coupling in the aortae of diabetic mice and in HG-treated human umbilical vein endothelial cells. (diabetesjournals.org)
- Together, these results suggest that CTRP13 preserves endothelial function in diabetic mice by regulating GCH1/BH4 axis-dependent eNOS coupling, suggesting the therapeutic potential of CTRP13 against diabetic vasculopathy. (diabetesjournals.org)
- Wołoszyn-Durkiewicz A, Myśliwiec M. The prognostic value of inflammatory and vascular endothelial dysfunction biomarkers in microvascular and macrovascular complications in type 1 diabetes. (termedia.pl)
- Prof. Wenzel, together with the Technische Universität München, the Institute of Pharmacology and Toxicology at the University of Bonn Hospital and the Physikalisch-Technische Bundesanstalt Berlin, developed a method with which damaged endothelial cells can regenerate and which they successfully tested in mice. (technologynetworks.com)
- After half an hour, the endothelial cells adhered so securely to the vascular wall that they could no longer be flushed away by the bloodstream," says Jun. (technologynetworks.com)
- Low-dose streptozotocin-induced diabetic mice exhibited increased aortic O-GlcNAcylation and vascular calcification, which was also associated with impaired aortic compliance in mice. (ahajournals.org)
- In type 2 diabetes-PAD patients, fetuin-A was inversely associated with mediasclerosis-the calcification process pathognomonic for diabetic PAD. (diabetesjournals.org)
- MMP10 treatment was more effective at reducing infarct size and neurodegeneration than tPA 24h and 3days after IS in diabetic mice. (unav.edu)
- 34 OPG-deficient mice develop severe medial and intimal arterial calcification in conjunction with high-turnover osteoporosis driven by excessive osteoclast formation. (ahajournals.org)
- Klotho-hypomorphic mice (kl/kl) suffer from severe vascular calcification and rapid aging. (nih.gov)
- Arterial stenosis occurs due to severe myointimal proliferation and reduced vascular elasticity, and can eventually lead to hypertension, myocardial ischemia and heart failure. (biologists.org)
- Fetuin-A knockout mice develop severe calcification of various organs ( 4 ). (diabetesjournals.org)
- In contrast, mice with CKD that were genetically engineered to have abnormally low levels of Klotho had worse kidney function and severe calcification. (healthcanal.com)
- The disease is characterized by extensive arterial calcification and stenosis of large- and medium-sized vessels, leading to vascular-related complications of hypertension and heart failure. (biologists.org)
- Background- Pulmonary arterial remodeling characterized by increased vascular smooth muscle proliferation is commonly seen in life-threatening disease, pulmonary arterial hypertension (PAH). (ahajournals.org)
- Currently, treatment of atherosclerosis includes reducing risk factors such as treatment of hypercholesterolemia and hypertension [ 1 , 2 ] and, for advanced disease, surgery such as stent implantation and bypass surgery using autologous vessels or tissue-engineered vascular grafts [ 5 ]. (thno.org)
- Female apoE −/− mice 8 wk of age (strain B6.129P2) on a C57BL/6J background were kept within the animal care facility of the University of Heidelberg (Heidelberg, Germany). (jimmunol.org)
- Methods and Results We measured calcification volume of aortic arch plaques using CNT-based micro-CT in 16- to 18-month-old males on 129S6/SvEvTac and C57BL/6J genetic backgrounds (129-apoE KO and B6-apoE KO). (ahajournals.org)
- Quantification from acquired images suggests higher susceptibility to calcification of the aortic arch plaques in 129-apoE KO than in B6-apoE KO mice. (ahajournals.org)
- Strains of mice that contain genetic disruptions (knockout) of APOLIPOPROTEINS E genes. (bioportfolio.com)
- A tissue-specific Knockout mouse defines an animal model in which a gene of interest is ' floxed ' and thus inactivatable in specific cell types in a certain tissue. (genoway.com)
- To clarify whether differences seen in both human patients and in animals models are due to ( a ) nature of individual mutations (e.g., hypomorphic variations in the Pten locus) or ( b ) genetic background/modifier genes, we generated two knockout mouse strains with different deletions and compared the consequences of Pten inactivation on 129/C57 and 129/BALB/c genetic backgrounds. (aacrjournals.org)
- The function of Fetuin-A in the body was determined by gene knockout technology in mice. (wikipedia.org)
- The calcification became drastically exacerbated when the fetuin-A knockout was combined with the genetic background DBA/2. (wikipedia.org)
- We are currently exploring downstream mechanisms by which vessel identity regulates vessel remodeling and the success or failure of vascular therapeutics (Sadaghianloo et al. (yale.edu)
- Whether teriparatide affects the progression of preexisting aortic calcification, widespread among this patient population, is unknown. (nih.gov)
- Widespread increased myeloid calcifying cells contribute to ectopic vascular calcification in type 2 diabetes. (bmj.com)
- Histological examination of placentas revealed cellular necrosis with mixed inflammation and calcification in the spongiotrophoblast layer and dysregulation of labyrinthine vascular development. (cdc.gov)