Myosins: A diverse superfamily of proteins that function as translocating proteins. They share the common characteristics of being able to bind ACTINS and hydrolyze MgATP. Myosins generally consist of heavy chains which are involved in locomotion, and light chains which are involved in regulation. Within the structure of myosin heavy chain are three domains: the head, the neck and the tail. The head region of the heavy chain contains the actin binding domain and MgATPase domain which provides energy for locomotion. The neck region is involved in binding the light-chains. The tail region provides the anchoring point that maintains the position of the heavy chain. The superfamily of myosins is organized into structural classes based upon the type and arrangement of the subunits they contain.Cardiac Myosins: Myosin type II isoforms found in cardiac muscle.Myosin Heavy Chains: The larger subunits of MYOSINS. The heavy chains have a molecular weight of about 230 kDa and each heavy chain is usually associated with a dissimilar pair of MYOSIN LIGHT CHAINS. The heavy chains possess actin-binding and ATPase activity.Myosin Subfragments: Parts of the myosin molecule resulting from cleavage by proteolytic enzymes (PAPAIN; TRYPSIN; or CHYMOTRYPSIN) at well-localized regions. Study of these isolated fragments helps to delineate the functional roles of different parts of myosin. Two of the most common subfragments are myosin S-1 and myosin S-2. S-1 contains the heads of the heavy chains plus the light chains and S-2 contains part of the double-stranded, alpha-helical, heavy chain tail (myosin rod).Myosin Light Chains: The smaller subunits of MYOSINS that bind near the head groups of MYOSIN HEAVY CHAINS. The myosin light chains have a molecular weight of about 20 KDa and there are usually one essential and one regulatory pair of light chains associated with each heavy chain. Many myosin light chains that bind calcium are considered "calmodulin-like" proteins.Myocarditis: Inflammatory processes of the muscular walls of the heart (MYOCARDIUM) which result in injury to the cardiac muscle cells (MYOCYTES, CARDIAC). Manifestations range from subclinical to sudden death (DEATH, SUDDEN). Myocarditis in association with cardiac dysfunction is classified as inflammatory CARDIOMYOPATHY usually caused by INFECTION, autoimmune diseases, or responses to toxic substances. Myocarditis is also a common cause of DILATED CARDIOMYOPATHY and other cardiomyopathies.Myosin Type II: The subfamily of myosin proteins that are commonly found in muscle fibers. Myosin II is also involved a diverse array of cellular functions including cell division, transport within the GOLGI APPARATUS, and maintaining MICROVILLI structure.Myocardium: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.Ventricular Myosins: Isoforms of MYOSIN TYPE II, specifically found in the ventricular muscle of the HEART. Defects in the genes encoding ventricular myosins result in FAMILIAL HYPERTROPHIC CARDIOMYOPATHY.Myocytes, Cardiac: Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC).Myosin Type V: A subclass of myosin involved in organelle transport and membrane targeting. It is abundantly found in nervous tissue and neurosecretory cells. The heavy chains of myosin V contain unusually long neck domains that are believed to aid in translocating molecules over large distances.Heart: The hollow, muscular organ that maintains the circulation of the blood.Sarcomeres: The repeating contractile units of the MYOFIBRIL, delimited by Z bands along its length.Actins: Filamentous proteins that are the main constituent of the thin filaments of muscle fibers. The filaments (known also as filamentous or F-actin) can be dissociated into their globular subunits; each subunit is composed of a single polypeptide 375 amino acids long. This is known as globular or G-actin. In conjunction with MYOSINS, actin is responsible for the contraction and relaxation of muscle.Actomyosin: A protein complex of actin and MYOSINS occurring in muscle. It is the essential contractile substance of muscle.Cardiomyopathy, Hypertrophic: A form of CARDIAC MUSCLE disease, characterized by left and/or right ventricular hypertrophy (HYPERTROPHY, LEFT VENTRICULAR; HYPERTROPHY, RIGHT VENTRICULAR), frequent asymmetrical involvement of the HEART SEPTUM, and normal or reduced left ventricular volume. Risk factors include HYPERTENSION; AORTIC STENOSIS; and gene MUTATION; (FAMILIAL HYPERTROPHIC CARDIOMYOPATHY).Myosin-Light-Chain Kinase: An enzyme that phosphorylates myosin light chains in the presence of ATP to yield myosin-light chain phosphate and ADP, and requires calcium and CALMODULIN. The 20-kDa light chain is phosphorylated more rapidly than any other acceptor, but light chains from other myosins and myosin itself can act as acceptors. The enzyme plays a central role in the regulation of smooth muscle contraction.Nonmuscle Myosin Type IIA: A nonmuscle isoform of myosin type II found predominantly in platelets, lymphocytes, neutrophils and brush border enterocytes.Tissue Plasminogen Activator: A proteolytic enzyme in the serine protease family found in many tissues which converts PLASMINOGEN to FIBRINOLYSIN. It has fibrin-binding activity and is immunologically different from UROKINASE-TYPE PLASMINOGEN ACTIVATOR. The primary sequence, composed of 527 amino acids, is identical in both the naturally occurring and synthetic proteases.Myosin Type I: A subclass of myosins found generally associated with actin-rich membrane structures such as filopodia. Members of the myosin type I family are ubiquitously expressed in eukaryotes. The heavy chains of myosin type I lack coiled-coil forming sequences in their tails and therefore do not dimerize.Nonmuscle Myosin Type IIB: A nonmuscle isoform of myosin type II found predominantly in neuronal tissue.Adenosine Triphosphatases: A group of enzymes which catalyze the hydrolysis of ATP. The hydrolysis reaction is usually coupled with another function such as transporting Ca(2+) across a membrane. These enzymes may be dependent on Ca(2+), Mg(2+), anions, H+, or DNA.Cardiac Output: The volume of BLOOD passing through the HEART per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with STROKE VOLUME (volume per beat).Myocardial Contraction: Contractile activity of the MYOCARDIUM.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Plasminogen Activator Inhibitor 1: A member of the serpin family of proteins. It inhibits both the tissue-type and urokinase-type plasminogen activators.Heart Ventricles: The lower right and left chambers of the heart. The right ventricle pumps venous BLOOD into the LUNGS and the left ventricle pumps oxygenated blood into the systemic arterial circulation.Urokinase-Type Plasminogen Activator: A proteolytic enzyme that converts PLASMINOGEN to FIBRINOLYSIN where the preferential cleavage is between ARGININE and VALINE. It was isolated originally from human URINE, but is found in most tissues of most VERTEBRATES.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Muscles: Contractile tissue that produces movement in animals.Autoimmune Diseases: Disorders that are characterized by the production of antibodies that react with host tissues or immune effector cells that are autoreactive to endogenous peptides.Actin Cytoskeleton: Fibers composed of MICROFILAMENT PROTEINS, which are predominately ACTIN. They are the smallest of the cytoskeletal filaments.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Myofibrils: The long cylindrical contractile organelles of STRIATED MUSCLE cells composed of ACTIN FILAMENTS; MYOSIN filaments; and other proteins organized in arrays of repeating units called SARCOMERES .Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Cardiomegaly: Enlargement of the HEART, usually indicated by a cardiothoracic ratio above 0.50. Heart enlargement may involve the right, the left, or both HEART VENTRICLES or HEART ATRIA. Cardiomegaly is a nonspecific symptom seen in patients with chronic systolic heart failure (HEART FAILURE) or several forms of CARDIOMYOPATHIES.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Cardiomyopathy, Hypertrophic, Familial: An autosomal dominant inherited form of HYPERTROPHIC CARDIOMYOPATHY. It results from any of more than 50 mutations involving genes encoding contractile proteins such as VENTRICULAR MYOSINS; cardiac TROPONIN T; ALPHA-TROPOMYOSIN.Ca(2+) Mg(2+)-ATPaseArrhythmias, Cardiac: Any disturbances of the normal rhythmic beating of the heart or MYOCARDIAL CONTRACTION. Cardiac arrhythmias can be classified by the abnormalities in HEART RATE, disorders of electrical impulse generation, or impulse conduction.Cardiac Surgical Procedures: Surgery performed on the heart.Kinetics: The rate dynamics in chemical or physical systems.Chickens: Common name for the species Gallus gallus, the domestic fowl, in the family Phasianidae, order GALLIFORMES. It is descended from the red jungle fowl of SOUTHEAST ASIA.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.Rats, Inbred LewDeath, Sudden, Cardiac: Unexpected rapid natural death due to cardiovascular collapse within one hour of initial symptoms. It is usually caused by the worsening of existing heart diseases. The sudden onset of symptoms, such as CHEST PAIN and CARDIAC ARRHYTHMIAS, particularly VENTRICULAR TACHYCARDIA, can lead to the loss of consciousness and cardiac arrest followed by biological death. (from Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 7th ed., 2005)Molecular Motor Proteins: Proteins that are involved in or cause CELL MOVEMENT such as the rotary structures (flagellar motor) or the structures whose movement is directed along cytoskeletal filaments (MYOSIN; KINESIN; and DYNEIN motor families).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).Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.Protein Isoforms: Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.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.Smooth Muscle Myosins: Myosin type II isoforms found in smooth muscle.Adenosine Triphosphate: An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.Cardiomyopathy, Dilated: A form of CARDIAC MUSCLE disease that is characterized by ventricular dilation, VENTRICULAR DYSFUNCTION, and HEART FAILURE. Risk factors include SMOKING; ALCOHOL DRINKING; HYPERTENSION; INFECTION; PREGNANCY; and mutations in the LMNA gene encoding LAMIN TYPE A, a NUCLEAR LAMINA protein.Myosin Type III: A subclass of myosins originally found in the photoreceptor of DROSOPHILA. The heavy chains can occur as two alternatively spliced isoforms of 132 and 174 KDa. The amino terminal of myosin type III is highly unusual in that it contains a protein kinase domain which may be an important component of the visual process.Tropomyosin: A protein found in the thin filaments of muscle fibers. It inhibits contraction of the muscle unless its position is modified by TROPONIN.Troponin I: One of the three polypeptide chains that make up the TROPONIN complex. It inhibits F-actin-myosin interactions.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Troponin: One of the minor protein components of skeletal muscle. Its function is to serve as the calcium-binding component in the troponin-tropomyosin B-actin-myosin complex by conferring calcium sensitivity to the cross-linked actin and myosin filaments.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.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Rheumatic Heart Disease: Cardiac manifestation of systemic rheumatological conditions, such as RHEUMATIC FEVER. Rheumatic heart disease can involve any part the heart, most often the HEART VALVES and the ENDOCARDIUM.Heterocyclic Compounds with 4 or More Rings: A class of organic compounds containing four or more ring structures, one of which is made up of more than one kind of atom, usually carbon plus another atom. The heterocycle may be either aromatic or nonaromatic.GizzardDisease 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.Swine: Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).Skeletal Muscle Myosins: Myosin type II isoforms found in skeletal muscle.Propylthiouracil: A thiourea antithyroid agent. Propythiouracil inhibits the synthesis of thyroxine and inhibits the peripheral conversion of throxine to tri-iodothyronine. It is used in the treatment of hyperthyroidism. (From Martindale, The Extra Pharmacopeoia, 30th ed, p534)Receptors, Urokinase Plasminogen Activator: An extracellular receptor specific for UROKINASE-TYPE PLASMINOGEN ACTIVATOR. It is attached to the cell membrane via a GLYCOSYLPHOSPHATIDYLINOSITOL LINKAGE and plays a role in the co-localization of urokinase-type plasminogen activator with PLASMINOGEN.Adrenergic beta-2 Receptor Antagonists: Drugs that bind to and block the activation of ADRENERGIC BETA-2 RECEPTORS.Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments.Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert PLASMINOGEN to FIBRINOLYSIN. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation.Mice, Transgenic: Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.Autoantibodies: Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.Dogs: The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)Heart Failure: A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.Cardiac Tamponade: Compression of the heart by accumulated fluid (PERICARDIAL EFFUSION) or blood (HEMOPERICARDIUM) in the PERICARDIUM surrounding the heart. The affected cardiac functions and CARDIAC OUTPUT can range from minimal to total hemodynamic collapse.Cardiac Pacing, Artificial: Regulation of the rate of contraction of the heart muscles by an artificial pacemaker.Myosin-Light-Chain Phosphatase: A phosphoprotein phosphatase that is specific for MYOSIN LIGHT CHAINS. It is composed of three subunits, which include a catalytic subunit, a myosin binding subunit, and a third subunit of unknown function.Heart Diseases: Pathological conditions involving the HEART including its structural and functional abnormalities.G(M2) Activator Protein: An essential cofactor for the degradation of G(M2)GANGLIOSIDE by lysosomal BETA-N-ACETYLHEXOSAMINIDASES. Genetic mutations resulting in loss of G(M2) activator protein are one of the causes of TAY-SACHS DISEASE, AB VARIANT.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.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.Heart Atria: The chambers of the heart, to which the BLOOD returns from the circulation.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Hyperthyroidism: Hypersecretion of THYROID HORMONES from the THYROID GLAND. Elevated levels of thyroid hormones increase BASAL METABOLIC RATE.Adenosine Diphosphate: Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Echocardiography: Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic.Cross Reactions: Serological reactions in which an antiserum against one antigen reacts with a non-identical but closely related antigen.Muscle, Smooth: Unstriated and unstriped muscle, one of the muscles of the internal organs, blood vessels, hair follicles, etc. Contractile elements are elongated, usually spindle-shaped cells with centrally located nuclei. Smooth muscle fibers are bound together into sheets or bundles by reticular fibers and frequently elastic nets are also abundant. (From Stedman, 25th ed)Cardiac Catheterization: Procedures in which placement of CARDIAC CATHETERS is performed for therapeutic or diagnostic procedures.Ventricular Function, Left: The hemodynamic and electrophysiological action of the left HEART VENTRICLE. Its measurement is an important aspect of the clinical evaluation of patients with heart disease to determine the effects of the disease on cardiac performance.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.Myocardial Infarction: NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).Animals, Newborn: Refers to animals in the period of time just after birth.Muscle Proteins: The protein constituents of muscle, the major ones being ACTINS and MYOSINS. More than a dozen accessory proteins exist including TROPONIN; TROPOMYOSIN; and DYSTROPHIN.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.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.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.Heart Arrest: Cessation of heart beat or MYOCARDIAL CONTRACTION. If it is treated within a few minutes, heart arrest can be reversed in most cases to normal cardiac rhythm and effective circulation.Microscopy, Electron: Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.Muscle, Skeletal: A subtype of striated muscle, attached by TENDONS to the SKELETON. Skeletal muscles are innervated and their movement can be consciously controlled. They are also called voluntary muscles.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Mice, Inbred C57BLCyclic AMP-Dependent Protein Kinases: A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.Enterovirus B, Human: A species of ENTEROVIRUS infecting humans and containing 36 serotypes. It is comprised of all the echoviruses and a few coxsackieviruses, including all of those previously named coxsackievirus B.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.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.Enzyme Activation: Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.Hypothyroidism: A syndrome that results from abnormally low secretion of THYROID HORMONES from the THYROID GLAND, leading to a decrease in BASAL METABOLIC RATE. In its most severe form, there is accumulation of MUCOPOLYSACCHARIDES in the SKIN and EDEMA, known as MYXEDEMA.Molecular Mimicry: The structure of one molecule that imitates or simulates the structure of a different molecule.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Coxsackievirus Infections: A heterogeneous group of infections produced by coxsackieviruses, including HERPANGINA, aseptic meningitis (MENINGITIS, ASEPTIC), a common-cold-like syndrome, a non-paralytic poliomyelitis-like syndrome, epidemic pleurodynia (PLEURODYNIA, EPIDEMIC) and a serious MYOCARDITIS.Thyroxine: The major hormone derived from the thyroid gland. Thyroxine is synthesized via the iodination of tyrosines (MONOIODOTYROSINE) and the coupling of iodotyrosines (DIIODOTYROSINE) in the THYROGLOBULIN. Thyroxine is released from thyroglobulin by proteolysis and secreted into the blood. Thyroxine is peripherally deiodinated to form TRIIODOTHYRONINE which exerts a broad spectrum of stimulatory effects on cell metabolism.Organ Specificity: Characteristic restricted to a particular organ of the body, such as a cell type, metabolic response or expression of a particular protein or antigen.Myoblasts, Cardiac: Precursor cells destined to differentiate into cardiac myocytes (MYOCYTES, CARDIAC).Protein Conformation: The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Plasminogen Activator Inhibitor 2: Member of the serpin family of proteins. It inhibits both the tissue-type and urokinase-type plasminogen activators.Dictyostelium: A genus of protozoa, formerly also considered a fungus. Its natural habitat is decaying forest leaves, where it feeds on bacteria. D. discoideum is the best-known species and is widely used in biomedical research.Molecular Weight: The sum of the weight of all the atoms in a molecule.Electrocardiography: Recording of the moment-to-moment electromotive forces of the HEART as projected onto various sites on the body's surface, delineated as a scalar function of time. The recording is monitored by a tracing on slow moving chart paper or by observing it on a cardioscope, which is a CATHODE RAY TUBE DISPLAY.Cloning, Molecular: The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.Cardiac Imaging Techniques: Visualization of the heart structure and cardiac blood flow for diagnostic evaluation or to guide cardiac procedures via techniques including ENDOSCOPY (cardiac endoscopy, sometimes refered to as cardioscopy), RADIONUCLIDE IMAGING; MAGNETIC RESONANCE IMAGING; TOMOGRAPHY; or ULTRASONOGRAPHY.Magnesium: A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.Turkeys: Large woodland game BIRDS in the subfamily Meleagridinae, family Phasianidae, order GALLIFORMES. Formerly they were considered a distinct family, Melegrididae.Ethylmaleimide: A sulfhydryl reagent that is widely used in experimental biochemical studies.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Plasminogen Inactivators: Important modulators of the activity of plasminogen activators. The inhibitors belong to the serpin family of proteins and inhibit both the tissue-type and urokinase-type plasminogen activators.Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by AUTOIMMUNE DISEASES.Heart Rate: The number of times the HEART VENTRICLES contract per unit of time, usually per minute.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.Cardiac Glycosides: Cyclopentanophenanthrenes with a 5- or 6-membered lactone ring attached at the 17-position and SUGARS attached at the 3-position. Plants they come from have long been used in congestive heart failure. They increase the force of cardiac contraction without significantly affecting other parameters, but are very toxic at larger doses. Their mechanism of action usually involves inhibition of the NA(+)-K(+)-EXCHANGING ATPASE and they are often used in cell biological studies for that purpose.Muscle Fibers, Skeletal: Large, multinucleate single cells, either cylindrical or prismatic in shape, that form the basic unit of SKELETAL MUSCLE. They consist of MYOFIBRILS enclosed within and attached to the SARCOLEMMA. They are derived from the fusion of skeletal myoblasts (MYOBLASTS, SKELETAL) into a syncytium, followed by differentiation.Hemodynamics: The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM.Cardiac Output, Low: A state of subnormal or depressed cardiac output at rest or during stress. It is a characteristic of CARDIOVASCULAR DISEASES, including congenital, valvular, rheumatic, hypertensive, coronary, and cardiomyopathic. The serious form of low cardiac output is characterized by marked reduction in STROKE VOLUME, and systemic vasoconstriction resulting in cold, pale, and sometimes cyanotic extremities.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.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.Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels.Sphingolipid Activator Proteins: A family of glycoprotein cofactors that are required for the efficient catabolization of SPHINGOLIPIDS by specific acid hydrolases such as GLUCOSYLCERAMIDASE; GALACTOCEREBROSIDASE; BETA-N-ACETYLHEXOSAMINIDASE; and CEREBROSIDE-SULFATASE.Ventricular Remodeling: The geometric and structural changes that the HEART VENTRICLES undergo, usually following MYOCARDIAL INFARCTION. It comprises expansion of the infarct and dilatation of the healthy ventricle segments. While most prevalent in the left ventricle, it can also occur in the right ventricle.rho-Associated Kinases: A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES.Out-of-Hospital Cardiac Arrest: Occurrence of heart arrest in an individual when there is no immediate access to medical personnel or equipment.DNA Primers: Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.Species Specificity: The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.Heart Transplantation: The transference of a heart from one human or animal to another.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.Cardiac Volume: The volume of the HEART, usually relating to the volume of BLOOD contained within it at various periods of the cardiac cycle. The amount of blood ejected from a ventricle at each beat is STROKE VOLUME.Cytoskeleton: The network of filaments, tubules, and interconnecting filamentous bridges which give shape, structure, and organization to the cytoplasm.Protein Structure, Tertiary: The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.Troponin T: One of the three polypeptide chains that make up the TROPONIN complex. It is a cardiac-specific protein that binds to TROPOMYOSIN. It is released from damaged or injured heart muscle cells (MYOCYTES, CARDIAC). Defects in the gene encoding troponin T result in FAMILIAL HYPERTROPHIC CARDIOMYOPATHY.Genes: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.Epitopes: Sites on an antigen that interact with specific antibodies.Regulatory Sequences, Nucleic Acid: Nucleic acid sequences involved in regulating the expression of genes.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Recombinant Fusion Proteins: Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.Blood Pressure: PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.Chemistry: A basic science concerned with the composition, structure, and properties of matter; and the reactions that occur between substances and the associated energy exchange.Mutation, Missense: A mutation in which a codon is mutated to one directing the incorporation of a different amino acid. This substitution may result in an inactive or unstable product. (From A Dictionary of Genetics, King & Stansfield, 5th ed)Heart Defects, Congenital: Developmental abnormalities involving structures of the heart. These defects are present at birth but may be discovered later in life.Chemical Phenomena: The composition, conformation, and properties of atoms and molecules, and their reaction and interaction processes.Mollusca: A phylum of the kingdom Metazoa. Mollusca have soft, unsegmented bodies with an anterior head, a dorsal visceral mass, and a ventral foot. Most are encased in a protective calcareous shell. It includes the classes GASTROPODA; BIVALVIA; CEPHALOPODA; Aplacophora; Scaphopoda; Polyplacophora; and Monoplacophora.Calmodulin-Binding Proteins: Proteins which bind calmodulin. They are found in many tissues and have a variety of functions including F-actin cross-linking properties, inhibition of cyclic nucleotide phosphodiesterase and calcium and magnesium ATPases.Aging: The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.Peptides: Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.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.Stroke Volume: The amount of BLOOD pumped out of the HEART per beat, not to be confused with cardiac output (volume/time). It is calculated as the difference between the end-diastolic volume and the end-systolic volume.Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Transcription Factor AP-1: A multiprotein complex composed of the products of c-jun and c-fos proto-oncogenes. These proteins must dimerize in order to bind to the AP-1 recognition site, also known as the TPA-responsive element (TRE). AP-1 controls both basal and inducible transcription of several genes.Cardiotonic Agents: Agents that have a strengthening effect on the heart or that can increase cardiac output. They may be CARDIAC GLYCOSIDES; SYMPATHOMIMETICS; or other drugs. They are used after MYOCARDIAL INFARCT; CARDIAC SURGICAL PROCEDURES; in SHOCK; or in congestive heart failure (HEART FAILURE).Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.Heart Function Tests: Examinations used to diagnose and treat heart conditions.Amoeba: A genus of ameboid protozoa. Characteristics include a vesicular nucleus and the formation of several lodopodia, one of which is dominant at a given time. Reproduction occurs asexually by binary fission.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.STAT3 Transcription Factor: A signal transducer and activator of transcription that mediates cellular responses to INTERLEUKIN-6 family members. STAT3 is constitutively activated in a variety of TUMORS and is a major downstream transducer for the CYTOKINE RECEPTOR GP130.Mice, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation.Plasminogen: Precursor of plasmin (FIBRINOLYSIN). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent.Heart Conduction System: An impulse-conducting system composed of modified cardiac muscle, having the power of spontaneous rhythmicity and conduction more highly developed than the rest of the heart.Point Mutation: A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.Cardiac Resynchronization Therapy: The restoration of the sequential order of contraction and relaxation of the HEART ATRIA and HEART VENTRICLES by atrio-biventricular pacing.Fibrinolysin: A product of the lysis of plasminogen (profibrinolysin) by PLASMINOGEN activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins.Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (CORONARY ARTERY DISEASE), to obstruction by a thrombus (CORONARY THROMBOSIS), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (MYOCARDIAL INFARCTION).Ventricular Dysfunction, Left: A condition in which the LEFT VENTRICLE of the heart was functionally impaired. This condition usually leads to HEART FAILURE; MYOCARDIAL INFARCTION; and other cardiovascular complications. Diagnosis is made by measuring the diminished ejection fraction and a depressed level of motility of the left ventricular wall.Protein Kinase C: An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.Cardiopulmonary Resuscitation: The artificial substitution of heart and lung action as indicated for HEART ARREST resulting from electric shock, DROWNING, respiratory arrest, or other causes. The two major components of cardiopulmonary resuscitation are artificial ventilation (RESPIRATION, ARTIFICIAL) and closed-chest CARDIAC MASSAGE.Heart Neoplasms: Tumors in any part of the heart. They include primary cardiac tumors and metastatic tumors to the heart. Their interference with normal cardiac functions can cause a wide variety of symptoms including HEART FAILURE; CARDIAC ARRHYTHMIAS; or EMBOLISM.Cardiac Care Facilities: Institutions specializing in the care of patients with heart disorders.Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.Fetal Heart: The heart of the fetus of any viviparous animal. It refers to the heart in the postembryonic period and is differentiated from the embryonic heart (HEART/embryology) only on the basis of time.Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.Protein Kinases: A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.Microscopy, Fluorescence: Microscopy of specimens stained with fluorescent dye (usually fluorescein isothiocyanate) or of naturally fluorescent materials, which emit light when exposed to ultraviolet or blue light. Immunofluorescence microscopy utilizes antibodies that are labeled with fluorescent dye.Hydrogen-Ion Concentration: The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Teerlink, JR (2009). "A novel approach to improve cardiac performance: cardiac myosin activators". Heart Fail Rev. 14 (4): 289- ... "Improvement of cardiac function by a cardiac myosin activator in conscious dogs with systolic heart failure". Circ Heart Fail. ... "The effects of the cardiac myosin activator, omecamtiv mecarbil, on cardiac function in systolic heart failure: a double-blind ... "Dose-dependent augmentation of cardiac systolic function with the selective cardiac myosin activator, omecamtiv mecarbil: a ...
Whereas MM-CK is expressed in sarcomeric muscle, that is, skeletal and cardiac muscle, MB-CK is expressed in cardiac muscle, ... substrate concentrations and activators.) This test is not specific for the type of CK that is elevated. ... such as acto-myosin ATPase and calcium ATPase involved in muscle contraction, and sodium/potassium ATPase involved in sodium ... cardiac, and smooth muscle contractility, and is involved in the generation of blood pressure. ...
The ratio of actin to myosin is between 2:1 and 10:1 in smooth muscle, compared to ~6:1 in skeletal muscle and 4:1 in cardiac ... In addition, it has been observed that most of the time there will be some cell to cell communication and activators/ ... Myosin is primarily class II in smooth muscle. Myosin II contains two heavy chains which constitute the head and tail domains. ... Myosin functions as an ATPase utilizing ATP to produce a molecular conformational change of part of the myosin and produces ...
Gupta MP, Gupta M, Dizon E, Zak R (1996). "Sympathetic control of cardiac myosin heavy chain gene expression". Molecular and ... Xia Y, Zhang YL, Yu C, Chang T, Fan HY (2014). "YAP/TEAD co-activator regulated pluripotency and chemoresistance in ovarian ... This recruitment leads to the repression of the MLC2v (Myosin Light Chain 2 v) and βMHC ( β-myosin heavy chain ) promoter. ... Regulation of myosin heavy chain genes, cardiac muscular genes troponin T and I Regulation of proliferation, Regulation of ...
Theoretically, a cardiac troponin activator could be useful for increasing cardiac contractility in the treatment of systolic ... sensitization of cardiac troponin C by positive feedback from force-generating myosin cross-bridges". Archives of Biochemistry ... In cardiac muscle, cTnC binds to cardiac troponin I (cTnI) and cardiac troponin T (cTnT), whereas cTnC binds to slow skeletal ... Troponin C is encoded by the TNNC1 gene in humans for both cardiac and slow skeletal muscle. Cardiac troponin C (cTnC) is a 161 ...
Downstream effectors of NRG-1/ErbB, include cardiac-specific myosin light chain kinase (cMLCK), Protein Phosphatase type 1 (PP1 ... a specific activator of p185erbB2". Science. 256 (5060): 1205-10. doi:10.1126/science.256.5060.1205. PMID 1350381. Orr-Urtreger ... "A cardiac myosin light chain kinase regulates sarcomere assembly in the vertebrate heart". J. Clin. Invest. 117 (10): 2812-24. ... "Identification of cardiac-specific myosin light chain kinase". Circ. Res. 102 (5): 571-80. doi:10.1161/CIRCRESAHA.107.161687. ...
... desmin and myosin light chain-2 exhibited changes in post-translational modifications. PKCε binds and phosphorylates cardiac ... Activation of PKCε with the specific activator, εRACK, prior to ischemic injury has shown to be associated with phosphorylation ... exhibited enhanced cardiac contractility. In addition to sarcomeres, PKCε also targets cardiac mitochondria. Proteomic analysis ... In cardiac muscle, PKCε translocates to sarcomeres at Z-lines following α-adrenergic and endothelin (ET)A-receptor stimulation ...
The activators also inhibit vascular smooth muscle cells from proliferation by blocking these cells' growth cycle and ... Furthermore, IP(-/-) mice on a high salt diet develop significantly higher levels of hypertension, cardiac fibrosis, and ... calmodulin-modulated myosin light chain kinase, RAF/MEK/Mitogen-activated protein kinases, PKC/Ca2+/Calcineurin/Nuclear factor ... IP activators inhibit the adherence of circulating platelets and leukocytes adherence to vascular endothelium thereby blocking ...
... myosin type i MeSH D08.811.277.040.025.525.750 --- myosin type ii MeSH D08.811.277.040.025.525.750.124 --- cardiac myosins MeSH ... urinary plasminogen activator MeSH D08.811.277.656.300.760.955 --- venombin a MeSH D08.811.277.656.300.760.955.060 --- ancrod ... myosin type iii MeSH D08.811.277.040.025.525.843 --- myosin type iv MeSH D08.811.277.040.025.525.875 --- myosin type v MeSH ... nonmuscle myosin type iia MeSH D08.811.277.040.025.525.750.500 --- nonmuscle myosin type iib MeSH D08.811.277.040.025.525. ...
The cardiac myosin binding protein C mutation identified in Maine Coon cats has not been found in any other breed of cat with ... Thrombolytic agents (e.g., tissue plasminogen activator) have been used with some success to break down an existing aortic ... The first genetic mutation (in cardiac myosin binding protein C) responsible for feline HCM was discovered in 2005 in Maine ... It fails to acknowledge the age at which relatives suffered sudden cardiac death, as well as the frequency of the cardiac ...
... ß activators and ligands and are found in higher levels in the tissues of patients affected with MFS. TGF-ß in its complex and ... The MYH11 gene is responsible for the smooth muscle myosin heavy chain and ACTA2 at TAAD4 loci encodes for smooth muscle alpha- ... "Elastogenesis at the onset of human cardiac valve development". Development. 140 (11): 2345-53. doi:10.1242/dev.093500. PMC ... "A novel fibrillin 1 gene mutation leading to marfan syndrome with minimal cardiac features". Molecular Syndromology. 5 (5): ...
... myosin phosphatase (MYPT), cardiac muscle troponin T (TnTc), etc. The retinoblastoma protein (pRb) and Cdc25 phosphatase were ... but their common upstream activator K-Ras protein is the one mutated. This "paradoxical" c-Raf activation necessitates the need ... "Phosphorylation of the myosin-binding subunit of myosin phosphatase by Raf-1 and inhibition of phosphatase activity". J. Biol. ... Pfleiderer P, Sumandea MP, Rybin VO, Wang C, Steinberg SF (2009). "Raf-1: a novel cardiac troponin T kinase". J. Muscle Res. ...
Cinaciguat, a sGC activator (not sGC stimulator). PDE5 inhibitors act downstream in the nitric oxide signalling pathway, ... This changes the actin-myosin contractility, which results in vasodilation. NO is produced by the enzyme endothelial nitric ... cardiac output and pulmonary arterial pressure compared to baseline values. In addition, a phase II study of riociguat is ... Evgenov OV, Pacher P, Schmidt PM, Haskó G, Schmidt HH, Stasch JP (September 2006). "NO-independent stimulators and activators ...
... eventually resulting in the dephosphorylation of the myosin light chain of the smooth muscle fiber. The subsequent ... Vasodilators used in cardiac diseases (C01D). Nitrovasodilators. *Nitroglycerin #. *Isosorbide dinitrate #. *Isosorbide ... Activators/stimulators: Ataciguat. *BAY 41-2272. *BAY 41-8543. *BAY 60-4552 ...
The activators also inhibit vascular smooth muscle cells from proliferation by blocking these cells' growth cycle and ... For example, the IP agonist iloprost is contraindicated in patients with unstable angina; decompensated cardiac failure (unless ... calmodulin-modulated myosin light chain kinase, RAF/MEK/Mitogen-activated protein kinases, PKC/Ca2+/Calcineurin/Nuclear factor ... IP activators inhibit the adherence of circulating platelets and leukocytes adherence to vascular endothelium thereby blocking ...
Recent studies have suggested that interferon-γ may serve as an activator of extracellular tTG in the small intestine; these ... tTG shows promise as a potential therapeutic target to treat cardiac fibrosis, through the activity of a highly selective tTG ... Evidence shows that intracellular tTG crosslinks itself to myosin. It is also believed that tTG may stabilize the structure of ... "Cardiac fibrosis can be attenuated by blocking the activity of transglutaminase 2 using a selective small-molecule inhibitor" ...
cardiac muscle contraction. • phosphorylation. • cellular response to sorbitol. • positive regulation of nitric-oxide synthase ... Myosin-heavy-chain kinase (EC 22.214.171.124). *Aurora kinase *Aurora A kinase ... "Purification and cDNA cloning of SAPKK3, the major activator of RK/p38 in stress- and cytokine-stimulated monocytes and ...
SDHD Cardiac arrhythmia, ankyrin-B-related; 600919; ANK2 Cardiac conduction defect, nonspecific; 612838; SCN1B ... KRT1 Plasminogen activator inhibitor, type I; 613329; PAI1 Platelet disorder, familial, with associated myeloid malignancy; ... myosin storage; 608358; MYH7 Myopathy, nemaline, 3; 161800; ACTA1 Myopathy, proximal, with early respiratory muscle involvement ... cardiac variant; 301500; GLA Factor V and factor VIII, combined deficiency of; 227300; MCFD2 Factor V deficiency; 227400; F5 ...
Force is generated in striated muscle by the interactions between myosin thick filaments and actin thin filaments. Liver ... "The SIRT1 activator SRT1720 extends lifespan and improves health of mice fed a standard diet". Cell Rep. 6 (5): 836-43. doi: ... skeletal and cardiac muscle. To understand the DNA damage theory of aging it is important to distinguish ... Chemical Carcinogenesis and Cardiac Hypertrophy: Experiments and Theory". Israel Journal of Medical Sciences. 13: 441. Sinha, ...
Myosin-heavy-chain kinase (EC 126.96.36.199). *Aurora kinase *Aurora A kinase ... Specific protein activators regulate the PIKK kinases but binding of them to the kinase complex causes a conformational change ... cardiac therapy/antianginals *Cardiac glycosides. *Antiarrhythmics. *Cardiac stimulants. *Antihypertensives. *Diuretics. * ...
The most important upstream activators of this pathway are the Raf proteins (A-Raf, B-Raf or c-Raf), the key mediators of ... Myosin-heavy-chain kinase (EC 188.8.131.52). *Aurora kinase *Aurora A kinase ... While also implicated in brain development, the embryonic lethality of ERK5 inactivation due to cardiac abnormalities ... Its sole specific upstream activator MKK5 is turned on in response to the MAP3 kinases MEKK2 and MEKK3. The specificity of ...
... and pulmonary hypertension before cardiac surgery". The Journal of Thoracic and Cardiovascular Surgery. 125 (3): 642-9. doi: ... PKA then continues the cascade by promoting the phosphorylation of the myosin light chain kinase, which inhibits it and leads ... and improves right ventricular stroke volume in patients undergoing cardiac surgery. A dose of 60 μg is hemodynamically safe, ...
... a novel cardiac myosin activator being developed for the potential treatment of patients with either acutely decompensated or ... are performing joint research focused on identifying and characterizing activators of cardiac myosin as back-up and follow-on ... Cytokinetics to Present Clinical Data on CK-1827452, a Selective Cardiac Myosin Activator, at the 2008 Heart Failure Congress ... Cytokinetics lead compound from this program, CK-1827452, a novel small molecule cardiac myosin activator, entered Phase II ...
Improvement of Cardiac Function by a Cardiac Myosin Activator in Conscious Dogs With Systolic Heart FailureClinical Perspective ... Improvement of Cardiac Function by a Cardiac Myosin Activator in Conscious Dogs With Systolic Heart FailureClinical Perspective ... Improvement of Cardiac Function by a Cardiac Myosin Activator in Conscious Dogs With Systolic Heart FailureClinical Perspective ... The cardiac myosin activator, CK-1827452, accelerates the enzymatic step gating entry of myosin into its force generating state ...
But phase II results with cardiac myosin activator need confirmation ... AHA: Cardiac Function Better in HFrEF With Novel Agent. - But phase II results with cardiac myosin activator need confirmation ... Omecamtiv is a selective cardiac myosin activator, which Teerlink described as "more hands pulling on the rope" for force ... "The trial showed it had effects on cardiac structure and function that are pretty much what you would have expected for a drug ...
Cardiac myosin activator. Additional relevant MeSH terms: Heart Failure. Ventricular Dysfunction, Left. Heart Diseases. ... molecule that increases cardiac contractility by selectively and directly activating the enzymatic domain of cardiac myosin ... COSMIC-HF - Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure. (COSMIC-HF). The safety and ... Chronic Oral Study of Myosin Activation to Increase Contractility in Heart Failure (COSMIC-HF): a phase 2, pharmacokinetic, ...
Zhou Y-C, Waxman DJ: Cross-talk between Janus kinase-signal transducer and activator of transcription (JAK-STAT) and peroxisome ... myosin heavy chain [MHC]-PPARα) were recently shown to exhibit increased rates of myocardial lipid oxidation, consistent with ... A: Basal cardiac palmitate uptake. B: Basal cardiac glucose uptake. C: Insulin-stimulated cardiac glucose uptake during ... To determine whether cardiac insulin resistance in the MHC-PPARα mice was associated with defects in cardiac insulin signaling ...
Cardiac myosin activator. • Increases entry rate of myosin into the tightly- bound, force-producing state with actin. • No ... Cardiac-fatigue, dizziness, ↓reserve • Hypotension. • Bradycardia-attenuate with ISA BBA --CI sev. brady, high degree AV block ... Block cardiac B-1 receptors. • Decrease heart rate/↑ diastolic filling • Decrease contractility/CO. • Reduce wall tension- ... cardiac metabolic action/fatty acid oxidation -- Reduce O2 Demand. • No effect on HR or BP. ...
Omecamtiv mecarbil is a novel cardiac myosin activator. Cardiac myosin is the cytoskeletal motor protein in the cardiac muscle ... Cardiac myosin activators are thought to accelerate the rate-limiting step of the myosin enzymatic cycle and shift the ... Improvement of Cardiac Function by a Cardiac Myosin Activator in Conscious Dogs With Systolic Heart Failure. Circ Heart Fail. ... Preclinical research has shown that cardiac myosin activators increase contractility in the absence of changes in intracellular ...
Omecamtiv mecarbil, a novel cardiac muscle myosin activator, has been the subject of a clinical trials program comprised of ... Omecamtiv mecarbil, a small-molecule, direct activator of cardiac myosin, was developed to address these limitations. ... The publication titled, "Cardiac Myosin Activation: A Potential Therapeutic Approach for Systolic Heart Failure," discusses the ... The authors concluded that cardiac myosin activation may provide a new therapeutic approach for patients with systolic heart ...
Omecamtiv MecarbilA Cardiac Myosin Activator. Preclinical. Selective activator of cardiac myosin. Prolongs duration of systole ... AHF and/or dyspnea from arrhythmias or non-cardiac causes, such as lung disease, anemia, or severe obesity ...
17922619 - Novel cardiac myosin activators for acute heart failure.. 25234549 - Managing antithrombotic therapy in patients ...
Heart, Failure, Renal, Insufficiency, Cardiac, Kidney, Hemodialysis, Impairment, omecamtiv mecarbil, cardiac myosin activator, ...
Cardiac myocyte explanation free. What is Cardiac myocyte? Meaning of Cardiac myocyte medical term. What does Cardiac myocyte ... Looking for online definition of Cardiac myocyte in the Medical Dictionary? ... Cytokinetics program is based on the hypothesis that activators of cardiac myosin may address certain mechanistic liabilities ... cardiac muscle. (redirected from Cardiac myocyte). Also found in: Dictionary, Thesaurus, Encyclopedia.. Related to Cardiac ...
... a previously discovered cardiac specific myosin activator (Malik et al., 2011), increases β-cardiac sS1 Fensemble generation as ... which is highly conserved among the cardiac myosins, from mouse α-cardiac to human β-cardiac myosin (Spudich, 2015). The mesa ... Human cardiomyopathy mutations are a leading cause of cardiac death. The human β-cardiac myosin motor is a major site in the ... 2011). Structure and interactions of myosin-binding protein C domain C0: cardiac-specific regulation of myosin at its neck? J. ...
MF] ATPase activator activity *[MF] actin binding *[MF] metal ion binding *[MF] myosin binding *[MF] myosin heavy chain binding ... BP] ventricular cardiac muscle tissue morphogenesis *[CC] A band *[CC] C zone *[CC] cytosol *[CC] sarcomere *[CC] striated ... BP] cardiac muscle contraction *[BP] cell adhesion *[BP] heart morphogenesis *[BP] muscle filament sliding *[BP] positive ... myosin binding protein C, cardiac. 9020536. Full Length. BC136546. myosin binding protein C, cardiac. ...
Teerlink, JR (2009). "A novel approach to improve cardiac performance: cardiac myosin activators". Heart Fail Rev. 14 (4): 289- ... "Improvement of cardiac function by a cardiac myosin activator in conscious dogs with systolic heart failure". Circ Heart Fail. ... "The effects of the cardiac myosin activator, omecamtiv mecarbil, on cardiac function in systolic heart failure: a double-blind ... "Dose-dependent augmentation of cardiac systolic function with the selective cardiac myosin activator, omecamtiv mecarbil: a ...
Cardiac Myosin Activator in Heart Failure. ?? ??/?? ?? 14:40-15:00. Diabetes and Heart Failure. Louise Burrell/. Melbourne Univ ... Clinical Benefits of Concomitant Maze During Cardiac Surgery. ???? /?? ??Ǵ 15:30-15:50. Stand-Alone Maze: When & How?. ?? / հ ... The Role of IGF-1 Receptor in Cardiac Remodeling. ?????/?? ??Ǵ 11:20-11:40. Vascular Injury Involves the Overoxidation of ... Current Positioning of Coronary CT Angiography in Ischemic Cardiac Disease. ??????/ ?? 14:20-14:40. SPECT or PET for Planning ...
Cardiac myosin activators.. However, in spite of all these possibilities and care processes, the most significant areas in ...
... selective cardiac myosin activator that binds to the catalytic domain of myosin. Preclinical research has shown that cardiac ... Improvement of cardiac function by a cardiac myosin activator in conscious dogs with systolic heart failure. Circ Heart Fail. ... 6-8 Cardiac myosin is the cytoskeletal motor protein in the cardiac muscle cell that is directly responsible for converting ... Mechanistic and structural basis for activation of cardiac myosin force production by omecamtiv mecarbil. Nat Commun. . 2017;8: ...
Cytokinetics develops first-in-class muscle activators as potential treatments for debilitating diseases in which muscle ... a cardiac myosin activator; reldesemtiv, a fast skeletal muscle troponin activator (FSTA); CK-274 and CK-271, cardiac myosin ... AMG 594 is an additional cardiac sarcomere activator discovered under the joint research program conducted between Amgen and ... a cardiac troponin activator; and CK-601, a next-generation FSTA. Our muscle biology drug discovery and development platform ...
... also known as a cardiac myotrope,1 being developed for the potential ... selective cardiac myosin activator, also known as a cardiac myotrope,1 that binds to the catalytic domain of myosin. ... Improvement of cardiac function by a cardiac myosin activator in conscious dogs with systolic heart failure. Circ Heart Fail. ... a novel selective cardiac myosin activator, also known as a cardiac myotrope,1 being developed for the potential treatment of ...
Today the company announced positive results from Phase IIa trials of cardiac myosin activator drug CK-1827452 for patients ...
Teerlink JR (2009) A novel approach to improve cardiac performance: cardiac myosin activators. Heart Fail Rev 14(4):289-298 ... The effects of the cardiac myosin activator, omecamtiv mecarbil, on cardiac function in systolic heart failure: a double-blind ... Dose-dependent augmentation of cardiac systolic function with the selective cardiac myosin activator, omecamtiv mecarbil: a ... Nagy L, Kovacs A, Bodi B, Pasztor ET, Fulop GA, Toth A et al (2015) The novel cardiac myosin activator omecamtiv mecarbil ...
Cardiac specific myosin ATPase activator €115.00 2251 Apoptozole Inhibitor of ATPase activity of Hsc70 and Hsp70 €95.00 ...
Cardiac specific myosin ATPase activator €115.00 2683 MYK-461 Cardiac specific myosin ATPase inhibitor €135.00 ... ATPase (myosin). Myosin (EC 184.108.40.206) and p97 (also known as Cdc48 or valosin containing protein (VCP; EC 220.127.116.11)) are both ... which binds the myosin to its cellular target. More than 35 classes of myosin have been discovered, 13 of which are represented ... Selective inhibitor of class II myosins; Active enantiomer of (±)-Blebbistatin €90.00 2718 Blebbistatin, (±)- Potent and ...
... and may require the use of inotropic drugs in patients with low cardiac output and evidence of organ hypoperfusion. However, ... the myosin activator omecamtiv mecarbil appears to have promising characteristics, while genetic therapy has been explored in ... Cardiac Output / physiology*. Cardiotonic Agents / adverse effects, pharmacology*. Clinical Trials as Topic. Digoxin / adverse ... 18273495 - Neuregulin-1 and its potential role in the control of cardiac function.. 17113395 - Pathophysiology of volume ...
MecarbilTroponin activatorATPaseSmall molecule cardiacImproved cardiac functionInhibitorActin and myosinMyocardialHeartIsoformsTherapeuticSkeletal muscle activatorsCytokineticsIncreasesAcuteDevelopment of cardiac hypertrophyMechanismFunctionPreclinicalAtrial natriuPharmacologicalClinical trialsContractileHeavy chainActivation
- In this investigation, we examined the effects of a novel cardiac myosin activator, omecamtiv mecarbil (formerly CK-1827452) in 2 different models of heart failure. (ahajournals.org)
- Omecamtiv mecarbil increased systolic function in sHF dogs, chronically instrumented to measure LV pressure, wall thickness, and cardiac output. (ahajournals.org)
- The major differences between the effect of omecamtiv mecarbil on cardiac function and the effect induced by a catecholamine, for example, dobutamine, is that omecamtiv mecarbil did not increase LV dP/dt but rather increased LV systolic ejection time by 26±2.9% in sHF. (ahajournals.org)
- This approach is made possible with the novel cardiac myosin-activating compound omecamtiv mecarbil (formerly called CK-1827452). (ahajournals.org)
- ORLANDO -- The novel agent omecamtiv mecarbil might improve cardiac contraction characteristics in heart failure with reduced ejection fraction (HFrEF), an early-phase study suggested. (medpagetoday.com)
- Omecamtiv mecarbil (AMG 423, CK-1827452) is a novel small molecule that increases cardiac contractility by selectively and directly activating the enzymatic domain of cardiac myosin heavy chain, the force-generating motor protein of the cardiac sarcomere. (clinicaltrials.gov)
- Cytokinetics, Incorporated (Nasdaq: CYTK) announced today the publication of preclinical research in the March 18, 2011 issue of the journal Science regarding the activation of cardiac myosin by an investigational drug candidate, omecamtiv mecarbil, and the potential therapeutic role that this novel mechanism may play for patients with systolic heart failure. (redorbit.com)
- This publication reveals, for the first time in a peer reviewed journal, the mechanism of action for omecamtiv mecarbil and the scientific rationale for directly modulating cardiac contractility as an innovative therapeutic strategy for improving cardiac performance in patients with heart failure. (redorbit.com)
- Omecamtiv mecarbil, a small-molecule, direct activator of cardiac myosin, was developed to address these limitations. (redorbit.com)
- In this publication, the authors demonstrated that omecamtiv mecarbil binds to the myosin catalytic domain and acts by an allosteric mechanism to increase the transition rate of myosin into the strongly actin-bound force-generating state. (redorbit.com)
- Paradoxically, omecamtiv mecarbil inhibits adenosine 5'-triphosphate (ATP) turnover in the absence of actin, which suggests that it stabilizes an actin-bound conformation of myosin. (redorbit.com)
- In animal models, omecamtiv mecarbil increases cardiac function by increasing the duration of ejection without changing the rates of cardiac contraction. (redorbit.com)
- Omecamtiv mecarbil, a novel cardiac muscle myosin activator, has been the subject of a clinical trials program comprised of multiple Phase I and Phase IIa trials conducted under Cytokinetics' sponsorship. (redorbit.com)
- 1 This first chronic dosing trial of omecamtiv mecarbil met its primary pharmacokinetic objective and demonstrated significant improvement in all pre-specified secondary measures of cardiac function in the treatment group employing pharmacokinetic-based dose titration. (oreanda.ru)
- Omecamtiv mecarbil is a novel cardiac myosin activator. (oreanda.ru)
- Omecamtiv mecarbil (INN), previously referred to as CK-1827452, is a cardiac-specific myosin activator. (wikipedia.org)
- Thus omecamtiv mecarbil improves systolic function by increasing the systolic ejection duration/stroke volume, without consuming more ATP energy, oxygen or altering intracellular calcium levels causing an overall improvement in cardiac efficiency. (wikipedia.org)
- Thus due to the unique cardiac myosin activation mechanism, omecamtiv mecarbil could safely improve cardiac function within tolerated doses. (wikipedia.org)
- THOUSAND OAKS, Calif. and SOUTH SAN FRANCISCO, Calif. , May 8, 2020 /PRNewswire/ -- Amgen (NASDAQ:AMGN) and Cytokinetics, Incorporated (NASDAQ:CYTK) today announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation for omecamtiv mecarbil, a novel selective cardiac myosin activator, also known as a cardiac myotrope, 1 being developed for the potential treatment of chronic heart failure with reduced ejection fraction (HFrEF). (yahoo.com)
- Omecamtiv mecarbil is a novel, selective cardiac myosin activator, also known as a cardiac myotrope, 1 that binds to the catalytic domain of myosin. (yahoo.com)
- Preclinical research has shown that omecamtiv mecarbil increases cardiac contractility without increasing intracellular myocyte calcium concentrations or myocardial oxygen consumption. (yahoo.com)
- Additionally, the myosin activator omecamtiv mecarbil appears to have promising characteristics, while genetic therapy has been explored in animal studies only. (biomedsearch.com)
- This includes new clinical and real-world studies that provide further evidence of the benefits of intensive lipid-lowering therapy with Repatha ® (evolocumab) as well as new data for omecamtiv mecarbil, a novel selective cardiac myosin activator being developed for the treatment of heart failure with reduced ejection fraction (HFrEF). (amgen.com)
- Cytokinetics is collaborating with Amgen Inc. (Amgen) to develop omecamtiv mecarbil , a novel cardiac muscle activator. (benzinga.com)
- In patients with HFrEF treated with omecamtiv mecarbil, in addition to previously reported improvements in cardiac contractility measures (including systolic function, or pumping action of the heart), measures of diastolic function were not different from placebo and, for some measures, trended towards improvement. (globenewswire.com)
- Earlier this month, Amgen announced that it will advance its cardiac myosin activator omecamtiv mecarbil into phase 3. (pharmaphorum.com)
- Omecamtiv mecarbil , a novel investigational cardiac myosin activator that increases cardiac contractility, is being developed by Amgen in collaboration with Cytokinetics for the potential treatment of heart failure. (oreanda.ru)
- It's encouraging to see in these data that patients' self-reported heart failure symptoms may have improved in association with improvements in cardiac function in those receiving omecamtiv mecarbil versus placebo," said Fady I. Malik, MD, PhD, Cytokinetics' Executive Vice President, Research and Development. (oreanda.ru)
- Amgen (AMGN) announced that it will present new data on omecamtiv mecarbil, a small molecule cardiac myosin activator that is being studied for the treatment of heart failure in collaboration with Cytokinetics. (bio-medicine.org)
- Data from the expansion phase showed that pharmacokinetic-based dose titration adequately controlled patient exposure to omecamtiv mecarbil and resulted in statistically significant decreases in cardiac dimensions and heart rate in the dose-titration group. (biomedreports.com)
- The primary objective of the trial was to assess the drug's safety and tolerability, with a secondary goal of evaluating the relationship between the plasma concentration of omecamtiv mecarbil and cardiac functions, to define concentrations for future trials. (technewslit.com)
- In addition, a new analysis of left atrial size and function from the COSMIC-HF ( C hronic O ral S tudy of M yosin Activation to I ncrease C ontractility in H eart F ailure) study evaluating omecamtiv mecarbil, a novel and investigational cardiac myosin activator for treatment of chronic heart failure, will be presented. (amgen.com)
- Expert Opin Drug Saf ;5: Omecamtiv mecarbil CKa cardiac myosin activator for heart failure. (cclap.me)
- We assessed the pharmacokinetics and effects on cardiac function and structure of the cardiac myosin activator, omecamtiv mecarbil. (edu.au)
- We assessed the maximum concentration of omecamtiv mecarbil in plasma ( primary endpoint ) and changes in cardiac function and ventricular diameters. (edu.au)
- Interpretation: Omecamtiv mecarbil dosing guided by pharmacokinetics achieved plasma concentrations associated with improved cardiac function and decreased ventricular diameter. (edu.au)
- Omecamtiv mecarbil (OM) is a compound that has been developed to treat systolic heart failure via targeting the cardiac myosin heavy chain to increase myocardial contractility. (unboundmedicine.com)
- TY - JOUR T1 - Omecamtiv Mecarbil Slows Myosin Kinetics in Skinned Rat Myocardium at Physiological Temperature. (unboundmedicine.com)
- The effects of the cardiac myosin activator, omecamtiv mecarbil, on cardiac function in systolic heart failure: a double-blind, placebo-controlled, crossover, dose-ranging phase 2 trial. (uni.lu)
- We report the first study of the cardiac myosin activator, omecamtiv mecarbil, in patients with systolic heart failure. (uni.lu)
- INTERPRETATION: Omecamtiv mecarbil improved cardiac function in patients with heart failure caused by left ventricular dysfunction and could be the first in class of a new therapeutic agent. (uni.lu)
- Cytokinetics is collaborating with Astellas Pharma Inc. (Astellas) to develop reldesemtiv , a fast skeletal muscle troponin activator (FSTA). (benzinga.com)
- CK-2017357 is a fast skeletal muscle troponin activator and is the lead drug candidate that has emerged from the company's skeletal sarcomere activator program. (marketwired.com)
- In collaboration with Astellas, Cytokinetics is developing reldesemtiv , a fast skeletal muscle troponin activator (FSTA), as a potential treatment for people with SMA and certain other debilitating diseases and conditions associated with skeletal muscle weakness and/or fatigue. (yahoo.com)
- Cytokinetics is collaborating with Astellas Pharma Inc. (Astellas) to develop reldesemtiv, a fast skeletal muscle troponin activator (FSTA) for diseases of neuromuscular dysfunction, including SMA and ALS. (advfn.com)
- Amgen recently started phase 1 trials of another Cytokinetics-developed heart failure candidate, cardiac troponin activator AMG 594. (pmlive.com)
- and Brad Morgan, SVP of Research and Non-Clinical Development will discuss progression of AMG 594, the cardiac troponin activator under our collaboration with Amgen and CK 377-3274 or CK 274, our unpartnered cardiac myosin inhibitor. (seekingalpha.com)
- So Fady will then come back and share updates on our skeletal muscle program focused on the development of reldesemtiv and the next generation [indiscernible] skeletal muscle troponin activator, we're advancing under our collaboration with Astellas. (seekingalpha.com)
- Having recently filed two INDs, one for CK-274 our unpartnered cardiac myosin inhibitor and one for AMG 594 our cardiac troponin activator discovered under our collaboration with Amgen were executing well on a purposeful strategy to augment our cardiac muscle programs and reinforce our demonstrated leadership in drug discovery and development relating to modulating the mechanics of cardiac muscle function focused to the potential treatment of cardiovascular diseases. (seekingalpha.com)
- AMG 594 is a novel, first-in-class, selective, oral, small molecule cardiac troponin activator, discovered under a joint research program with Amgen . (cytokinetics.com)
- The Structural Basis of the Myosin ATPase Activity. (axonmedchem.com)
- Activation of PKC in cardiac muscle cells by phorbol esters has been shown to phosphorylate myofibrillar proteins, 9 10 11 12 resulting in changes in the sensitivity of the myofilaments to Ca 2+ 11 and/or changes in V max of the actomyosin ATPase. (ahajournals.org)
- In vitro it binds MHC, F-actin and native thin filaments, and modifies the activity of actin-activated myosin ATPase. (mybiosource.com)
- Measurement of calcium activated myosin ATPase activity when bound to thin filaments. (cytoskeleton.com)
- The purified myosin S1 fragment has been determined to be biologically active in an F-actin activated ATPase assay (see biological activity assay). (cytoskeleton.com)
- Cytokinetics' lead compound from this program, CK-1827452, a novel small molecule cardiac myosin activator, entered Phase II clinical trials for the treatment of heart failure in 2007. (marketwired.com)
- CK-274 is a novel, oral, small molecule cardiac myosin inhibitor that company scientists discovered independent of its collaborations. (cytokinetics.com)
- The concept is that we have improved cardiac function and actually been able to intervene in this vicious cycle of progressive worsening heart function, which begets neurohormonal activation, which begets bad remodeling," he said. (medpagetoday.com)
- Furthermore, we demonstrated that GAS6 activated the mitogen-activated protein kinase kinase 1/2-extracellular signal-regulated kinase 1/2 pathway during pressure overload-induced cardiac hypertrophy, and the pharmacological mitogen-activated protein kinase kinase 1/2 inhibitor U0126 almost completely reversed GAS6 overexpression-induced cardiac hypertrophy and fibrosis, resulting in improved cardiac function. (ahajournals.org)
- I (J.A.S.) was asked to preface my talk at the 2015 Journal of Experimental Biology Symposium on Muscle: Molecules to Motion with a brief historical perspective of my laboratory's specific contributions to research on actin and myosin, and how those contributions led to our current focus on understanding the molecular basis of hypertrophic and dilated cardiomyopathy. (biologists.org)
- Mice with heart-specific overexpression of PPARα (myosin heavy chain [MHC]-PPARα) were recently shown to exhibit increased rates of myocardial lipid oxidation, consistent with the role of PPARα ( 10 ). (diabetesjournals.org)
- Importantly, MHC-PPARα mice developed cardiomyopathy with enhanced sensitivity to myocardial ischemic insult, and these functional/structural changes were associated with reduced expression of genes involved in cardiac glucose utilization ( 10 ). (diabetesjournals.org)
- Within the past decade considerable advances have been made in identifying the genetic basis of myocardial disorders such as familial hypertrophic cardiomyopathy and dilated cardiomyopathy, as well as the molecular signalling pathways and gene regulatory events that characterise acquired disease such as pressure overload induced cardiac hypertrophy. (bmj.com)
- ICU patients frequently develop low output syndromes due to cardiac dysfunction, myocardial injury, and inflammatory activation. (resus.me)
- Independent prognostic value of serum creatine kinase isoenzyme MB mass, cardiac troponin T and myosin light chain levels in suspected acute myocardial infarction: analysis of 28 months of follow-up in 196 patients. (rawmilkinstitute.org)
- Comparison of invasive and conservative strategies after treatment with intravenous tissue plasminogen activator in acute myocardial infarction. (rawmilkinstitute.org)
- Late Breaking Trials: "The Selective Cardiac Myosin Activator, CK-1827452, Increases Systolic Function in Heart Failure" (Oral Presentation 564a on Monday, June 16, 2008, during the Late Breaking Trials session, 11:00 a.m. - 12:30 p.m. (marketwired.com)
- Left ventricular stroke volume, ejection fraction, and fractional shortening were also improved along with cardiac dimensions, they reported here at the American Heart Association meeting . (medpagetoday.com)
- Diabetic heart failure may be causally associated with alterations in cardiac energy metabolism and insulin resistance. (diabetesjournals.org)
- Mice with heart-specific overexpression of peroxisome proliferator-activated receptor (PPAR)α showed a metabolic and cardiomyopathic phenotype similar to the diabetic heart, and we determined tissue-specific glucose metabolism and insulin action in vivo during hyperinsulinemic-euglycemic clamps in awake myosin heavy chain (MHC)-PPARα mice (12-14 weeks of age). (diabetesjournals.org)
- Basal and insulin-stimulated glucose uptake in heart was significantly reduced in the MHC-PPARα mice, and cardiac insulin resistance was mostly attributed to defects in insulin-stimulated activities of insulin receptor substrate (IRS)-1-associated phosphatidylinositol (PI) 3-kinase, Akt, and tyrosine phosphorylation of signal transducer and activator of transcription 3 (STAT3). (diabetesjournals.org)
- Overall, these findings indicate that increased activity of PPARα, as occurs in the diabetic heart, leads to cardiac insulin resistance associated with defects in insulin signaling and STAT3 activity, subsequently leading to reduced cardiac function. (diabetesjournals.org)
- Although the etiology of diabetic heart failure is poorly understood, there is a growing body of evidence ( 3 - 5 ) indicating that alterations in cardiac energy metabolism may precede and be causally associated with the development of cardiomyopathy in the diabetic heart. (diabetesjournals.org)
- The publication titled, "Cardiac Myosin Activation: A Potential Therapeutic Approach for Systolic Heart Failure," discusses the potential clinical role for therapies that directly activate cardiac myosin in the treatment of systolic heart failure. (redorbit.com)
- The authors concluded that cardiac myosin activation may provide a new therapeutic approach for patients with systolic heart failure. (redorbit.com)
- CK 1827452 ( Axon 1835 ), is an agent that directly activates myosin, for use in the treatment of heart failure. (axonmedchem.com)
- The prevalence of heart failure is growing with our aging demographics, and GALACTIC-HF is designed to assess the clinical effects of our novel myosin activator in patients meaningfully at risk. (yahoo.com)
- In 2006, Amgen and Cytokinetics entered into a strategic alliance to discover, develop, and commercialize novel small molecule therapeutics designed to activate cardiac muscle for the potential treatment of heart failure. (cytokinetics.com)
- The pathophysiologic processes behind remodelling in heart failure are complex and reflect systemic neurohormonal activation, peripheral vascular effects and localised changes affecting the cardiac substrate. (springer.com)
- Novel therapy targeted at improving cardiac contractile mechanics in HFrEF hold the promise of alleviating heart failure at its source, yet so far none has found success. (springer.com)
- Today the company announced positive results from Phase IIa trials of cardiac myosin activator drug CK-1827452 for patients with stable heart failure. (247wallst.com)
- Thus, phosphorylation of cardiac myofilaments by AA and/or ET, in addition to phosphorylation-dependent inhibition of distinct K + channels, may represent an important signaling pathway by which AA and ET influence the inotropic state of the heart. (ahajournals.org)
- MYBPC3, the cardiac isoform, is expressed exclussively in heart muscle. (mybiosource.com)
- Acute heart failure with low cardiac output: can we develop a short-term inotropic agent that does not increase adverse events? (biomedsearch.com)
- Acute heart failure represents an increasingly common cause of hospitalization, and may require the use of inotropic drugs in patients with low cardiac output and evidence of organ hypoperfusion. (biomedsearch.com)
- Further investigations are needed to confirm and expand the effectiveness and safety of these agents in patients with acute heart failure and low cardiac output. (biomedsearch.com)
- This new class of drugs, known as cardiac myosin activators, helps tune the mechanics of the heart muscle," Dr. Forgacs says. (evms.edu)
- The interaction between the drug and the cardiac motor that powers the heart provided insights into the mechanism of drug action that control the motor," she says. (evms.edu)
- Our structural analysis defines a drug-binding site that may be exploited for development of medication with enhanced ability to modulate cardiac output and treat heart disease. (evms.edu)
- Prior to that, at Cytokinetics, she established and led the cell biology and pharmacology efforts to identity and develop a myosin activator therapeutic for heart failure, and at Genentech, identified therapeutics for endocrine and cardiac indications. (prnewswire.com)
- In mid-stage trials omecamtiv has produced dose-dependent increases in various measures of cardiac function that are compromised in heart failure, including systolic ejection time (SET), stroke volume (SV), left ventricular ejection fraction (LVEF), and fractional shortening. (pmlive.com)
- As you will hear from Fady in a moment, there is still a very large unmet need for the treatment of heart failure and related diseases of cardiac muscle dysfunction as resonated quite loudly at the Heart Failure Society of American Meetings which we attended during the past quarter. (seekingalpha.com)
- Individuals who have cardiac hypertrophy and cardiomyopathies are predisposed to the development of heart failure ( Yu, 2013 and references therein). (sdbonline.org)
- CLP-1 is expressed very early, prior to cardiac fate assignment, in development and its expression, based on in situ hybridization, coincides remarkably well with the established morphogenetic field of early heart formation. (downstate.edu)
- CLP-1 is expressed and co-localized along with the components of p-TEFb complex in developing heart during the period in which the knockout mice lacking the CLP-1 gene develop cardiac hypertrophy. (downstate.edu)
- Our findings suggest that strategies to reduce GAS6 activity in cardiac tissue may be a novel approach to attenuate the development of congestive heart failure. (ahajournals.org)
- Cardiac hypertrophy, which is commonly observed in hypertension, ischemia, and valvular heart disease, is an adaptive response to long-standing biomechanical pressure or volume overload. (ahajournals.org)
- Aldosteronism in Heart Failure: A Proinflammatory / Fibrogenic Cardiac Phenotype. (eurekaselect.com)
- Cinaciguat prevented structural, molecular alterations and improved cardiac performance of the diabetic heart. (biomedcentral.com)
- It acts as an independent risk factor for coronary atherosclerosis and ischemic heart disease, however, the altered metabolic state-due to elevated glucose levels-has a direct impact on cardiac structure and function independently of coronary artery disease. (biomedcentral.com)
- One of the major issues hindering the development of new therapies has been difficulties in developing appropriate in vitro model systems of human heart failure that recapitulate the essential changes in cardiac mechanics seen in the disease. (frontiersin.org)
- HF is characterized by the inability of the heart to generate sufficient cardiac output to effectively pump blood to the body under normal physiological pressures. (frontiersin.org)
- in phase-2a studies in patients with systolic heart failure it demonstrated improved stroke volume without an increase in heart rate, although cardiac ischaemia emerged at high plasma concentrations 4,5 . (resus.me)
- 6 We have reported that the production of ET-1 is markedly increased both in the hypertrophied heart and the failing heart 11-14 and that chronic treatment with ET type A receptor antagonists significantly inhibited the development of cardiac hypertrophy and heart failure. (ahajournals.org)
- 11,13,14 These data suggest that ET-1 plays an important role in the development of cardiac hypertrophy and heart failure, both in vitro and in vivo. (ahajournals.org)
- To assess the acute and chronic effects of PEPs on cardiac physiology, male Sprague Dawley rats were exposed to PEPs (21 days, 5 h/day) while monitoring LV pressure (LVP) and electrocardiogram (ECG) via conscious telemetry, analyzing LVP and heart rate variability (HRV) in four-day increments from exposure days 1 to 21, as well as ECG and baroreflex sensitivity. (biomedcentral.com)
- Multiple lines of experimental and clinical evidence have suggested the importance of the Gqα-phosphoinositide signaling system in the development of pathological cardiac hypertrophy and heart failure. (ahajournals.org)
- Epinephrine, norepinephrine, angiotensin II, and aldosterone have been identified as the most important neurohormones stimulating stress-mediated or reactive cardiac hypertrophy, i.e., pathological hypertrophy, and contributing to its progression to heart failure. (jci.org)
- DCM can progress to heart failure and severe complications such as stroke, arrhythmias, and sudden cardiac death. (myokardia.com)
- A heart and smooth muscle-specific SRF co-activator, myocardin, has been shown to be required for cardiac development and smooth muscle differentiation. (mendeley.com)
- While finite element models of the heart can naturally account for patient-specific anatomies reconstructed from medical images, optimizing the many other parameters driving simulated cardiac functions is challenging due to computational complexity. (prelekara.sk)
- Multi-scale, tailor-made heart simulation can predict the effect of cardiac resynchronization therapy. (prelekara.sk)
- 7. Moin DS, Sackheim J, Hamo CE, Butler J. Cardiac Myosin Activators in Systolic Heart Failure: More Friend than Foe? (prelekara.sk)
- Multiple cAMP phosphodiesterase (PDE) isoforms play divergent roles in cardiac homeostasis but the molecular basis for their non-redundant function remains poorly understood. (biologists.org)
- MHC: cardiac isoforms MHCa, MHCb. (mitomap.org)
- 4 MLC genes are expressed in rodents: MLC1F, MLC3F in adult fast SKM, MLC1V and MLC1A are cardiac isoforms also expressed in adult slow and fetal SKM. (mitomap.org)
- In smooth muscle, there is a single gene (MYH11) that codes for the heavy chains myosin II, but there are splice variants of this gene that result in four distinct isoforms. (wikipedia.org)
- Alpha actin is also expressed as distinct genetic isoforms such as smooth muscle, cardiac muscle and skeletal muscle specific isoforms of alpha actin. (wikipedia.org)
- In non-clinical models, skeletal sarcomere activators have demonstrated pharmacological activity that may lead to new therapeutic options for diseases associated with aging, muscle wasting, and neuromuscular dysfunction. (marketwired.com)
- 2 , 3 Therefore, molecules that selectively affect these signaling pathways may have therapeutic potential in pathological cardiac hypertrophy. (ahajournals.org)
- In 2013, Astellas and Cytokinetics formed a partnership focused on the research, development, and commercialization of skeletal muscle activators. (cytokinetics.com)
- The companies agreed to amend their collaboration agreement to enable the development of reldesemtiv for the potential treatment of ALS and to extend their joint research focused on the discovery of additional next-generation skeletal muscle activators through 2017. (cytokinetics.com)
- Under a strategic alliance established in 2006, Cytokinetics and Amgen Inc. are performing joint research focused on identifying and characterizing activators of cardiac myosin as back-up and follow-on potential drug candidates to CK-1827452. (marketwired.com)
- It is our honor to have Cytokinetics' novel scientific research into direct modulators of the cardiac contractile apparatus published in this prestigious journal," stated Fady I. Malik, MD, FACC, Cytokinetics' Vice President of Biology and Therapeutics and lead author of this report. (redorbit.com)
- Cytokinetics is a late-stage biopharmaceutical company focused on discovering, developing, and commercializing first-in-class muscle activators and best-in-class muscle inhibitors as potential treatments for people with debilitating diseases in which muscle performance is compromised and/or declining. (cytokinetics.com)
- AMG 594 is an additional cardiac sarcomere activator discovered under the joint research program conducted between Amgen and Cytokinetics scientists. (cytokinetics.com)
- In April 2020, Cytokinetics and Astellas agreed to amend the collaboration, providing Cytokinetics exclusive control and responsibility for the development and commercialization of reldesemtiv , CK-601 and other fast skeletal regulatory activator (FSRA) compounds. (cytokinetics.com)
- Cytokinetics is a late-stage biopharmaceutical company focused on discovering, developing and commercializing first-in-class muscle activators and best-in-class muscle inhibitors as potential treatments for debilitating diseases in which muscle performance is compromised and/or declining. (benzinga.com)
- The candidate has been developed with Cytokinetics, which showed benefits to cardiac function in its COSMIC-HF phase 2 study. (pharmaphorum.com)
- This first-time-in-humans clinical trial of CK-2017357 builds on our expertise in the biology of muscle function, initially demonstrated with our cardiac muscle myosin activator program and now translated to our skeletal sarcomere activator program," stated Fady Malik, MD, PhD, Cytokinetics' Vice President, Biology and Therapeutics. (marketwired.com)
- Cytokinetics is a late-stage biopharmaceutical company focused on discovering, developing, and commercializing first-in-class muscle activators. (cytokinetics.com)
- Some recent patents discuss the role of cardiac hormones, especially focus on natriuretic peptide for the treatment of acute coronary syndrome. (eurekaselect.com)
- In an acute cardiac care setting, short-term use of inotropic agents is crucial for the restoration of arterial blood pressure and peripheral tissue perfusion, as well as weaning of cardiosurgery. (resus.me)
- The trial showed it had effects on cardiac structure and function that are pretty much what you would have expected for a drug with this mechanism of action. (medpagetoday.com)
- Despite numerous studies, most performed with non-human or non-cardiac myosin, there is no clear consensus about the mechanism of action of these mutations on the function of human β-cardiac myosin. (biologists.org)
- Structural and Functional Insights into the Myosin Motor Mechanism. (axonmedchem.com)
- Cardiac hypertrophy is a compensatory mechanism in response to a variety of cardiovascular diseases. (aspetjournals.org)
- Cardiac hypertrophy marked by cell enlargement without proliferation is a compensatory mechanism in response to a variety of cardiovascular diseases ( Bueno and Molkentin, 2002 ). (aspetjournals.org)
- Despite mounting studies, the underlying molecular mechanism of pathological cardiac hypertrophy is still poorly understood. (ahajournals.org)
- The simple elegance of this mechanism and the obligatory role of Ca 2+ in activation have contributed to the perception that Ca 2+ binding to TnC composes the entirety of regulation in vertebrate skeletal and cardiac muscles, and yet, some properties of regulation cannot be explained without invoking additional processes. (rupress.org)
- And now if we can stop that perhaps we can reverse remodel, decrease neurohormonal activation, and perhaps get back to maintaining better cardiac function. (medpagetoday.com)
- Insulin-stimulated cardiac glucose uptake was similarly reduced in 8-week-old MHC-PPARα mice without changes in cardiac function and hepatic insulin action compared with the age-matched wild-type littermates. (diabetesjournals.org)
- Since normal cardiac function is dependent on a constant rate of ATP resynthesis predominantly driven by mitochondrial fatty acid oxidation, activation of PPARα by endogenous ligands, such as fatty acids, plays an important role in cardiac energy metabolism and functions ( 8 , 9 ). (diabetesjournals.org)
- In this review, we examine HFrEF therapy aimed at improving cardiac function with a focus on recent trials and emerging targets. (springer.com)
- Recent studies in cardiac muscle cells have suggested that arachidonic acid (AA) may be an important signaling molecule in the modulation of cardiac contractile function via alterations in Ca 2+ cycling. (ahajournals.org)
- The study met its primary pharmacokinetic objective and showed statistically significant improvements in all pre-specified secondary measures of cardiac function in the treatment group receiving pharmacokinetic-based dose titration. (oreanda.ru)
- By directly improving skeletal muscle function, a small molecule activator of the skeletal sarcomere may potentially enhance physical performance and quality of life in patients with conditions marked by muscle weakness, including neuromuscular diseases such as amyotrophic lateral sclerosis (ALS), myasthenia gravis, cachexia, sarcopenia and the general frailty associated with aging. (marketwired.com)
- We expect that Amgen will initiate a Phase 1 program for AMG 594 before the end of the year to assess its safety, tolerability, pharmacokinetics and its potential to increase cardiac function in healthy volunteers. (cytokinetics.com)
- We expect to initiate a Phase 1 program for CK-274 before the end of the year to assess its safety, tolerability, pharmacokinetics and its effect on cardiac function in healthy volunteers. (cytokinetics.com)
- Indeed, we know of no studies that examine cardiac function in burbot. (biologists.org)
- A myosin activator improves actin assembly and sarcomere function of human-induced pluripotent stem cell-derived cardiomyocytes with a troponin T point mutation. (abcam.com)
- Its exact function is unclear, but it's believed that it contributes to the structural stability of the myosin head along with MLC20. (wikipedia.org)
- In primaries, slow, heavy chain myosin expressing (MHCbeta), embryonic MHC (MHCemb) and sometimes low amounts of perinantal (MHCpn) are expressed. (mitomap.org)
- and, wherein the transplanted skeletal myoblasts are left to engraft and exhibit skeletal myosin heavy chain positive staining from three weeks post-transplantation. (epo.org)
- The long term maintenance of the skeletal cell fate was confirmed by staining with anti-skeletal myosin heavy chain antibody beginning at three weeks post implantation. (epo.org)
- may be useful in postmyocardial infarction cardiac dysfunction and septic shock through increasing coronary flow and attenuating inflammatory activation, respectively 2 . (resus.me)
- The most recommended inotropes in this condition are levosimendan and dobutamine (both class of recommendation: IIa, level of evidence: B). Recent data indicate that levosimendan may be useful in postmyocardial infarction cardiac dysfunction and septic shock through increasing coronary flow and attenuating inflammatory activation, respectively. (resus.me)
- We hypothesized that DGK might prevent GPCR agonist-induced activation of diacylglycerol downstream signaling cascades and subsequent cardiac hypertrophy. (ahajournals.org)
- We hypothesized that DGKζ may act as a negative regulator for GPCR agonist-induced activation of the DAG-PKC signaling cascade and subsequent cardiac hypertrophy in vivo. (ahajournals.org)