Lipoproteins: Lipid-protein complexes involved in the transportation and metabolism of lipids in the body. They are spherical particles consisting of a hydrophobic core of TRIGLYCERIDES and CHOLESTEROL ESTERS surrounded by a layer of hydrophilic free CHOLESTEROL; PHOSPHOLIPIDS; and APOLIPOPROTEINS. Lipoproteins are classified by their varying buoyant density and sizes.Lipoproteins, LDL: A class of lipoproteins of small size (18-25 nm) and light (1.019-1.063 g/ml) particles with a core composed mainly of CHOLESTEROL ESTERS and smaller amounts of TRIGLYCERIDES. The surface monolayer consists mostly of PHOSPHOLIPIDS, a single copy of APOLIPOPROTEIN B-100, and free cholesterol molecules. The main LDL function is to transport cholesterol and cholesterol esters to extrahepatic tissues.Lipoproteins, HDL: A class of lipoproteins of small size (4-13 nm) and dense (greater than 1.063 g/ml) particles. HDL lipoproteins, synthesized in the liver without a lipid core, accumulate cholesterol esters from peripheral tissues and transport them to the liver for re-utilization or elimination from the body (the reverse cholesterol transport). Their major protein component is APOLIPOPROTEIN A-I. HDL also shuttle APOLIPOPROTEINS C and APOLIPOPROTEINS E to and from triglyceride-rich lipoproteins during their catabolism. HDL plasma level has been inversely correlated with the risk of cardiovascular diseases.Lipoproteins, VLDL: A class of lipoproteins of very light (0.93-1.006 g/ml) large size (30-80 nm) particles with a core composed mainly of TRIGLYCERIDES and a surface monolayer of PHOSPHOLIPIDS and CHOLESTEROL into which are imbedded the apolipoproteins B, E, and C. VLDL facilitates the transport of endogenously made triglycerides to extrahepatic tissues. As triglycerides and Apo C are removed, VLDL is converted to INTERMEDIATE-DENSITY LIPOPROTEINS, then to LOW-DENSITY LIPOPROTEINS from which cholesterol is delivered to the extrahepatic tissues.Lipoprotein Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. The enzyme hydrolyzes triacylglycerols in chylomicrons, very-low-density lipoproteins, low-density lipoproteins, and diacylglycerols. It occurs on capillary endothelial surfaces, especially in mammary, muscle, and adipose tissue. Genetic deficiency of the enzyme causes familial hyperlipoproteinemia Type I. (Dorland, 27th ed) EC 3.1.1.34.Lipoprotein(a): A lipoprotein that resembles the LOW-DENSITY LIPOPROTEINS but with an extra protein moiety, APOPROTEIN (A) also known as APOLIPOPROTEIN (A), linked to APOLIPOPROTEIN B-100 on the LDL by one or two disulfide bonds. High plasma level of lipoprotein (a) is associated with increased risk of atherosclerotic cardiovascular disease.Receptors, Virus: Specific molecular components of the cell capable of recognizing and interacting with a virus, and which, after binding it, are capable of generating some signal that initiates the chain of events leading to the biological response.Receptors, Immunologic: Cell surface molecules on cells of the immune system that specifically bind surface molecules or messenger molecules and trigger changes in the behavior of cells. Although these receptors were first identified in the immune system, many have important functions elsewhere.Integrins: A family of transmembrane glycoproteins (MEMBRANE GLYCOPROTEINS) consisting of noncovalent heterodimers. They interact with a wide variety of ligands including EXTRACELLULAR MATRIX PROTEINS; COMPLEMENT, and other cells, while their intracellular domains interact with the CYTOSKELETON. The integrins consist of at least three identified families: the cytoadhesin receptors(RECEPTORS, CYTOADHESIN), the leukocyte adhesion receptors (RECEPTORS, LEUKOCYTE ADHESION), and the VERY LATE ANTIGEN RECEPTORS. Each family contains a common beta-subunit (INTEGRIN BETA CHAINS) combined with one or more distinct alpha-subunits (INTEGRIN ALPHA CHAINS). These receptors participate in cell-matrix and cell-cell adhesion in many physiologically important processes, including embryological development; HEMOSTASIS; THROMBOSIS; WOUND HEALING; immune and nonimmune defense mechanisms; and oncogenic transformation.Receptors, Lipoprotein: Cell surface proteins that bind lipoproteins with high affinity. Lipoprotein receptors in the liver and peripheral tissues mediate the regulation of plasma and cellular cholesterol metabolism and concentration. The receptors generally recognize the apolipoproteins of the lipoprotein complex, and binding is often a trigger for endocytosis.Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils.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.Cell Line: Established cell cultures that have the potential to propagate indefinitely.TriglyceridesApolipoproteins: Protein components on the surface of LIPOPROTEINS. They form a layer surrounding the hydrophobic lipid core. There are several classes of apolipoproteins with each playing a different role in lipid transport and LIPID METABOLISM. These proteins are synthesized mainly in the LIVER and the INTESTINES.Apolipoproteins B: Major structural proteins of triacylglycerol-rich LIPOPROTEINS. There are two forms, apolipoprotein B-100 and apolipoprotein B-48, both derived from a single gene. ApoB-100 expressed in the liver is found in low-density lipoproteins (LIPOPROTEINS, LDL; LIPOPROTEINS, VLDL). ApoB-48 expressed in the intestine is found in CHYLOMICRONS. They are important in the biosynthesis, transport, and metabolism of triacylglycerol-rich lipoproteins. Plasma Apo-B levels are high in atherosclerotic patients but non-detectable in ABETALIPOPROTEINEMIA.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.Lipoproteins, HDL3: Intermediate-density subclass of the high-density lipoproteins, with particle sizes between 7 to 8 nm. As the larger lighter HDL2 lipoprotein, HDL3 lipoprotein is lipid-rich.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.Receptors, Cell Surface: Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.Lipoproteins, IDL: A mixture of very-low-density lipoproteins (VLDL), particularly the triglyceride-poor VLDL, with slow diffuse electrophoretic mobilities in the beta and alpha2 regions which are similar to that of beta-lipoproteins (LDL) or alpha-lipoproteins (HDL). They can be intermediate (remnant) lipoproteins in the de-lipidation process, or remnants of mutant CHYLOMICRONS and VERY-LOW-DENSITY LIPOPROTEINS which cannot be metabolized completely as seen in FAMILIAL DYSBETALIPOPROTEINEMIA.Receptors, LDL: Receptors on the plasma membrane of nonhepatic cells that specifically bind LDL. The receptors are localized in specialized regions called coated pits. Hypercholesteremia is caused by an allelic genetic defect of three types: 1, receptors do not bind to LDL; 2, there is reduced binding of LDL; and 3, there is normal binding but no internalization of LDL. In consequence, entry of cholesterol esters into the cell is impaired and the intracellular feedback by cholesterol on 3-hydroxy-3-methylglutaryl CoA reductase is lacking.Cell Adhesion: Adherence of cells to surfaces or to other cells.Mice, Inbred C57BLRNA, 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.Lipoproteins, HDL2: Low-density subclass of the high-density lipoproteins, with particle sizes between 8 to 13 nm.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.Cholesterol, HDL: Cholesterol which is contained in or bound to high-density lipoproteins (HDL), including CHOLESTEROL ESTERS and free cholesterol.Ligands: A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)Lipids: A generic term for fats and lipoids, the alcohol-ether-soluble constituents of protoplasm, which are insoluble in water. They comprise the fats, fatty oils, essential oils, waxes, phospholipids, glycolipids, sulfolipids, aminolipids, chromolipids (lipochromes), and fatty acids. (Grant & Hackh's Chemical Dictionary, 5th ed)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.Cholesterol, LDL: Cholesterol which is contained in or bound to low density lipoproteins (LDL), including CHOLESTEROL ESTERS and free cholesterol.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Reverse Transcriptase Polymerase Chain Reaction: A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.Cholesterol Esters: Fatty acid esters of cholesterol which constitute about two-thirds of the cholesterol in the plasma. The accumulation of cholesterol esters in the arterial intima is a characteristic feature of atherosclerosis.Apolipoproteins E: A class of protein components which can be found in several lipoproteins including HIGH-DENSITY LIPOPROTEINS; VERY-LOW-DENSITY LIPOPROTEINS; and CHYLOMICRONS. Synthesized in most organs, Apo E is important in the global transport of lipids and cholesterol throughout the body. Apo E is also a ligand for LDL receptors (RECEPTORS, LDL) that mediates the binding, internalization, and catabolism of lipoprotein particles in cells. There are several allelic isoforms (such as E2, E3, and E4). Deficiency or defects in Apo E are causes of HYPERLIPOPROTEINEMIA TYPE III.Chylomicrons: A class of lipoproteins that carry dietary CHOLESTEROL and TRIGLYCERIDES from the SMALL INTESTINE to the tissues. Their density (0.93-1.006 g/ml) is the same as that of VERY-LOW-DENSITY LIPOPROTEINS.Low Density Lipoprotein Receptor-Related Protein-1: A LDL-receptor related protein involved in clearance of chylomicron remnants and of activated ALPHA-MACROGLOBULINS from plasma.Apolipoproteins A: Structural proteins of the alpha-lipoproteins (HIGH DENSITY LIPOPROTEINS), including APOLIPOPROTEIN A-I and APOLIPOPROTEIN A-II. They can modulate the activity of LECITHIN CHOLESTEROL ACYLTRANSFERASE. These apolipoproteins are low in atherosclerotic patients. They are either absent or present in extremely low plasma concentration in TANGIER DISEASE.Apolipoprotein B-100: A 513-kDa protein synthesized in the LIVER. It serves as the major structural protein of low-density lipoproteins (LIPOPROTEINS, LDL; LIPOPROTEINS, VLDL). It is the ligand for the LDL receptor (RECEPTORS, LDL) that promotes cellular binding and internalization of LDL particles.Hyperlipidemias: Conditions with excess LIPIDS in the blood.Cholesterol, VLDL: Cholesterol which is contained in or bound to very low density lipoproteins (VLDL). High circulating levels of VLDL cholesterol are found in HYPERLIPOPROTEINEMIA TYPE IIB. The cholesterol on the VLDL is eventually delivered by LOW-DENSITY LIPOPROTEINS to the tissues after the catabolism of VLDL to INTERMEDIATE-DENSITY LIPOPROTEINS, then to LDL.Ultracentrifugation: Centrifugation with a centrifuge that develops centrifugal fields of more than 100,000 times gravity. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Arteriosclerosis: Thickening and loss of elasticity of the walls of ARTERIES of all sizes. There are many forms classified by the types of lesions and arteries involved, such as ATHEROSCLEROSIS with fatty lesions in the ARTERIAL INTIMA of medium and large muscular arteries.Apolipoproteins C: A group of apolipoproteins that can readily exchange among the various classes of lipoproteins (HDL; VLDL; CHYLOMICRONS). After lipolysis of TRIGLYCERIDES on VLDL and chylomicrons, Apo-C proteins are normally transferred to HDL. The subtypes can modulate remnant binding to receptors, LECITHIN CHOLESTEROL ACYLTRANSFERASE, or LIPOPROTEIN LIPASE.Hypercholesterolemia: A condition with abnormally high levels of CHOLESTEROL in the blood. It is defined as a cholesterol value exceeding the 95th percentile for the population.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Lipase: An enzyme of the hydrolase class that catalyzes the reaction of triacylglycerol and water to yield diacylglycerol and a fatty acid anion. It is produced by glands on the tongue and by the pancreas and initiates the digestion of dietary fats. (From Dorland, 27th ed) EC 3.1.1.3.Apolipoprotein B-48: A 241-kDa protein synthesized only in the INTESTINES. It serves as a structural protein of CHYLOMICRONS. Its exclusive association with chylomicron particles provides an indicator of intestinally derived lipoproteins in circulation. Apo B-48 is a shortened form of apo B-100 and lacks the LDL-receptor region.Apolipoprotein A-II: The second most abundant protein component of HIGH DENSITY LIPOPROTEINS or HDL. It has a high lipid affinity and is known to displace APOLIPOPROTEIN A-I from HDL particles and generates a stable HDL complex. ApoA-II can modulate the activation of LECITHIN CHOLESTEROL ACYLTRANSFERASE in the presence of APOLIPOPROTEIN A-I, thus affecting HDL metabolism.Cholesterol, Dietary: Cholesterol present in food, especially in animal products.Hypertriglyceridemia: A condition of elevated levels of TRIGLYCERIDES in the blood.Lipid Metabolism: Physiological processes in biosynthesis (anabolism) and degradation (catabolism) of LIPIDS.Hyperlipoproteinemias: Conditions with abnormally elevated levels of LIPOPROTEINS in the blood. They may be inherited, acquired, primary, or secondary. Hyperlipoproteinemias are classified according to the pattern of lipoproteins on electrophoresis or ultracentrifugation.Hyperlipoproteinemia Type II: A group of familial disorders characterized by elevated circulating cholesterol contained in either LOW-DENSITY LIPOPROTEINS alone or also in VERY-LOW-DENSITY LIPOPROTEINS (pre-beta lipoproteins).Apolipoprotein C-II: A 9-kDa protein component of VERY-LOW-DENSITY LIPOPROTEINS. It contains a cofactor for LIPOPROTEIN LIPASE and activates several triacylglycerol lipases. The association of Apo C-II with plasma CHYLOMICRONS; VLDL, and HIGH-DENSITY LIPOPROTEINS is reversible and changes rapidly as a function of triglyceride metabolism. Clinically, Apo C-II deficiency is similar to lipoprotein lipase deficiency (HYPERLIPOPROTEINEMIA TYPE I) and is therefore called hyperlipoproteinemia type IB.Apolipoprotein C-III: A 9-kDa protein component of VERY-LOW-DENSITY LIPOPROTEINS and CHYLOMICRON REMNANTS. Apo C-III, synthesized in the liver, is an inhibitor of LIPOPROTEIN LIPASE. Apo C-III modulates the binding of chylomicron remnants and VLDL to receptors (RECEPTORS, LDL) thus decreases the uptake of triglyceride-rich particles by the liver cells and subsequent degradation. The normal Apo C-III is glycosylated. There are several polymorphic forms with varying amounts of SIALIC ACID (Apo C-III-0, Apo C-III-1, and Apo C-III-2).Cholesterol Ester Transfer Proteins: Proteins that bind to and transfer CHOLESTEROL ESTERS between LIPOPROTEINS such as LOW-DENSITY LIPOPROTEINS and HIGH-DENSITY LIPOPROTEINS.Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides see GLYCEROPHOSPHOLIPIDS) or sphingosine (SPHINGOLIPIDS). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system.Phosphatidylcholine-Sterol O-Acyltransferase: An enzyme secreted from the liver into the plasma of many mammalian species. It catalyzes the esterification of the hydroxyl group of lipoprotein cholesterol by the transfer of a fatty acid from the C-2 position of lecithin. In familial lecithin:cholesterol acyltransferase deficiency disease, the absence of the enzyme results in an excess of unesterified cholesterol in plasma. EC 2.3.1.43.Atherosclerosis: A thickening and loss of elasticity of the walls of ARTERIES that occurs with formation of ATHEROSCLEROTIC PLAQUES within the ARTERIAL INTIMA.Apoprotein(a): A large and highly glycosylated protein constituent of LIPOPROTEIN (A). It has very little affinity for lipids but forms disulfide-linkage to APOLIPOPROTEIN B-100. Apoprotein(a) has SERINE PROTEINASE activity and can be of varying sizes from 400- to 800-kDa. It is homologous to PLASMINOGEN and is known to modulate THROMBOSIS and FIBRINOLYSIS.Dietary Fats: Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados.Scavenger Receptors, Class B: A family of scavenger receptors that are predominately localized to CAVEOLAE of the PLASMA MEMBRANE and bind HIGH DENSITY LIPOPROTEINS.Receptors, Scavenger: A large group of structurally diverse cell surface receptors that mediate endocytic uptake of modified LIPOPROTEINS. Scavenger receptors are expressed by MYELOID CELLS and some ENDOTHELIAL CELLS, and were originally characterized based on their ability to bind acetylated LOW-DENSITY LIPOPROTEINS. They can also bind a variety of other polyanionic ligand. Certain scavenger receptors can internalize micro-organisms as well as apoptotic cells.Kinetics: The rate dynamics in chemical or physical systems.Particle Size: Relating to the size of solids.Hyperlipoproteinemia Type I: An inherited condition due to a deficiency of either LIPOPROTEIN LIPASE or APOLIPOPROTEIN C-II (a lipase-activating protein). The lack of lipase activities results in inability to remove CHYLOMICRONS and TRIGLYCERIDES from the blood which has a creamy top layer after standing.Hyperlipoproteinemia Type IV: A hypertriglyceridemia disorder, often with autosomal dominant inheritance. It is characterized by the persistent elevations of plasma TRIGLYCERIDES, endogenously synthesized and contained predominantly in VERY-LOW-DENSITY LIPOPROTEINS (pre-beta lipoproteins). In contrast, the plasma CHOLESTEROL and PHOSPHOLIPIDS usually remain within normal limits.Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Anticholesteremic Agents: Substances used to lower plasma CHOLESTEROL levels.Triolein: (Z)-9-Octadecenoic acid 1,2,3-propanetriyl ester.Macrophages: The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood MONOCYTES. Main types are PERITONEAL MACROPHAGES; ALVEOLAR MACROPHAGES; HISTIOCYTES; KUPFFER CELLS of the liver; and OSTEOCLASTS. They may further differentiate within chronic inflammatory lesions to EPITHELIOID CELLS or may fuse to form FOREIGN BODY GIANT CELLS or LANGHANS GIANT CELLS. (from The Dictionary of Cell Biology, Lackie and Dow, 3rd ed.)Hypolipidemic Agents: Substances that lower the levels of certain LIPIDS in the BLOOD. They are used to treat HYPERLIPIDEMIAS.Heparin: A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts.Foam Cells: Lipid-laden macrophages originating from monocytes or from smooth muscle cells.Antigens, CD36: Leukocyte differentiation antigens and major platelet membrane glycoproteins present on MONOCYTES; ENDOTHELIAL CELLS; PLATELETS; and mammary EPITHELIAL CELLS. They play major roles in CELL ADHESION; SIGNAL TRANSDUCTION; and regulation of angiogenesis. CD36 is a receptor for THROMBOSPONDINS and can act as a scavenger receptor that recognizes and transports oxidized LIPOPROTEINS and FATTY ACIDS.Scavenger Receptors, Class E: A class of oxidized LDL receptors that contain LECTIN-like extracellular domains.Lipolysis: The metabolic process of breaking down LIPIDS to release FREE FATTY ACIDS, the major oxidative fuel for the body. Lipolysis may involve dietary lipids in the DIGESTIVE TRACT, circulating lipids in the BLOOD, and stored lipids in the ADIPOSE TISSUE or the LIVER. A number of enzymes are involved in such lipid hydrolysis, such as LIPASE and LIPOPROTEIN LIPASE from various tissues.Hypolipoproteinemias: Conditions with abnormally low levels of LIPOPROTEINS in the blood. This may involve any of the lipoprotein subclasses, including ALPHA-LIPOPROTEINS (high-density lipoproteins); BETA-LIPOPROTEINS (low-density lipoproteins); and PREBETA-LIPOPROTEINS (very-low-density lipoproteins).Dyslipidemias: Abnormalities in the serum levels of LIPIDS, including overproduction or deficiency. Abnormal serum lipid profiles may include high total CHOLESTEROL, high TRIGLYCERIDES, low HIGH DENSITY LIPOPROTEIN CHOLESTEROL, and elevated LOW DENSITY LIPOPROTEIN CHOLESTEROL.Fatty Acids: Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated (FATTY ACIDS, UNSATURATED). (Grant & Hackh's Chemical Dictionary, 5th ed)Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Hyperlipoproteinemia Type III: An autosomal recessively inherited disorder characterized by the accumulation of intermediate-density lipoprotein (IDL or broad-beta-lipoprotein). IDL has a CHOLESTEROL to TRIGLYCERIDES ratio greater than that of VERY-LOW-DENSITY LIPOPROTEINS. This disorder is due to mutation of APOLIPOPROTEINS E, a receptor-binding component of VLDL and CHYLOMICRONS, resulting in their reduced clearance and high plasma levels of both cholesterol and triglycerides.Abetalipoproteinemia: An autosomal recessive disorder of lipid metabolism. It is caused by mutation of the microsomal triglyceride transfer protein that catalyzes the transport of lipids (TRIGLYCERIDES; CHOLESTEROL ESTERS; PHOSPHOLIPIDS) and is required in the secretion of BETA-LIPOPROTEINS (low density lipoproteins or LDL). Features include defective intestinal lipid absorption, very low serum cholesterol level, and near absent LDL.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.Esterification: The process of converting an acid into an alkyl or aryl derivative. Most frequently the process consists of the reaction of an acid with an alcohol in the presence of a trace of mineral acid as catalyst or the reaction of an acyl chloride with an alcohol. Esterification can also be accomplished by enzymatic processes.Apoproteins: The protein components of a number of complexes, such as enzymes (APOENZYMES), ferritin (APOFERRITINS), or lipoproteins (APOLIPOPROTEINS).Risk Factors: An aspect of personal behavior or lifestyle, environmental exposure, or inborn or inherited characteristic, which, on the basis of epidemiologic evidence, is known to be associated with a health-related condition considered important to prevent.Hydroxymethylglutaryl-CoA Reductase Inhibitors: Compounds that inhibit HMG-CoA reductases. They have been shown to directly lower cholesterol synthesis.Apolipoprotein C-I: A 6.6-kDa protein component of VERY-LOW-DENSITY LIPOPROTEINS; INTERMEDIATE-DENSITY LIPOPROTEINS; and HIGH-DENSITY LIPOPROTEINS. Apo C-I displaces APO E from lipoproteins, modulate their binding to receptors (RECEPTORS, LDL), and thereby decrease their clearance from plasma. Elevated Apo C-I levels are associated with HYPERLIPOPROTEINEMIA and ATHEROSCLEROSIS.Apolipoprotein E3: A 34-kDa glycosylated protein. A major and most common isoform of apolipoprotein E. Therefore, it is also known as apolipoprotein E (ApoE). In human, Apo E3 is a 299-amino acid protein with a cysteine at the 112 and an arginine at the 158 position. It is involved with the transport of TRIGLYCERIDES; PHOSPHOLIPIDS; CHOLESTEROL; and CHOLESTERYL ESTERS in and out of the cells.Biological Transport: The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.Lymph: The interstitial fluid that is in the LYMPHATIC SYSTEM.Aryldialkylphosphatase: An enzyme which catalyzes the hydrolysis of an aryl-dialkyl phosphate to form dialkyl phosphate and an aryl alcohol. It can hydrolyze a broad spectrum of organophosphate substrates and a number of aromatic carboxylic acid esters. It may also mediate an enzymatic protection of LOW DENSITY LIPOPROTEINS against oxidative modification and the consequent series of events leading to ATHEROMA formation. The enzyme was previously regarded to be identical with Arylesterase (EC 3.1.1.2).LDL-Receptor Related Proteins: A family of proteins that share sequence similarity with the low density lipoprotein receptor (RECEPTORS, LDL).Hyperlipidemia, Familial Combined: A type of familial lipid metabolism disorder characterized by a variable pattern of elevated plasma CHOLESTEROL and/or TRIGLYCERIDES. Multiple genes on different chromosomes may be involved, such as the major late transcription factor (UPSTREAM STIMULATORY FACTORS) on CHROMOSOME 1.Coronary Disease: An imbalance between myocardial functional requirements and the capacity of the CORONARY VESSELS to supply sufficient blood flow. It is a form of MYOCARDIAL ISCHEMIA (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels.Hydroxymethylglutaryl CoA Reductases: Enzymes that catalyze the reversible reduction of alpha-carboxyl group of 3-hydroxy-3-methylglutaryl-coenzyme A to yield MEVALONIC ACID.Aorta: The main trunk of the systemic arteries.Oleic Acid: An unsaturated fatty acid that is the most widely distributed and abundant fatty acid in nature. It is used commercially in the preparation of oleates and lotions, and as a pharmaceutical solvent. (Stedman, 26th ed)Sterol O-Acyltransferase: An enzyme that catalyzes the formation of cholesterol esters by the direct transfer of the fatty acid group from a fatty acyl CoA derivative. This enzyme has been found in the adrenal gland, gonads, liver, intestinal mucosa, and aorta of many mammalian species. EC 2.3.1.26.Electrophoresis, Agar Gel: Electrophoresis in which agar or agarose gel is used as the diffusion medium.Oleic Acids: A group of fatty acids that contain 18 carbon atoms and a double bond at the omega 9 carbon.Fasting: Abstaining from all food.ATP Binding Cassette Transporter 1: A superfamily of large integral ATP-binding cassette membrane proteins whose expression pattern is consistent with a role in lipid (cholesterol) efflux. It is implicated in TANGIER DISEASE characterized by accumulation of cholesteryl ester in various tissues.Phosphatidylcholines: Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to a choline moiety. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid and choline and 2 moles of fatty acids.Lecithin Acyltransferase Deficiency: An autosomal recessively inherited disorder caused by mutation of LECITHIN CHOLESTEROL ACYLTRANSFERASE that facilitates the esterification of lipoprotein cholesterol and subsequent removal from peripheral tissues to the liver. This defect results in low HDL-cholesterol level in blood and accumulation of free cholesterol in tissue leading to a triad of CORNEAL OPACITY, hemolytic anemia (ANEMIA, HEMOLYTIC), and PROTEINURIA.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Adipose Tissue: Specialized connective tissue composed of fat cells (ADIPOCYTES). It is the site of stored FATS, usually in the form of TRIGLYCERIDES. In mammals, there are two types of adipose tissue, the WHITE FAT and the BROWN FAT. Their relative distributions vary in different species with most adipose tissue being white.Tangier Disease: An autosomal recessively inherited disorder caused by mutation of ATP-BINDING CASSETTE TRANSPORTERS involved in cellular cholesterol removal (reverse-cholesterol transport). It is characterized by near absence of ALPHA-LIPOPROTEINS (high-density lipoproteins) in blood. The massive tissue deposition of cholesterol esters results in HEPATOMEGALY; SPLENOMEGALY; RETINITIS PIGMENTOSA; large orange tonsils; and often sensory POLYNEUROPATHY. The disorder was first found among inhabitants of Tangier Island in the Chesapeake Bay, MD.Probucol: A drug used to lower LDL and HDL cholesterol yet has little effect on serum-triglyceride or VLDL cholesterol. (From Martindale, The Extra Pharmacopoeia, 30th ed, p993).Postprandial Period: The time frame after a meal or FOOD INTAKE.Diet, Atherogenic: A diet that contributes to the development and acceleration of ATHEROGENESIS.Lovastatin: A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver.Phospholipid Transfer Proteins: A ubiquitous family of proteins that transport PHOSPHOLIPIDS such as PHOSPHATIDYLINOSITOL and PHOSPHATIDYLCHOLINE between membranes. They play an important role in phospholipid metabolism during vesicular transport and SIGNAL TRANSDUCTION.Blood Protein Electrophoresis: Electrophoresis applied to BLOOD PROTEINS.LDL-Receptor Related Protein-Associated Protein: A membrane protein found in the rough endoplasm reticulum (ENDOPLASMIC RETICULUM, ROUGH) that binds to LDL-RECEPTOR RELATED PROTEINS. It may function to prevent ligand binding of receptors during protein processing events within endosomal compartments.High-Density Lipoproteins, Pre-beta: A highly dense subclass of the high-density lipoproteins, with particle sizes below 7 nm. They are also known as nascent HDL, composed of a few APOLIPOPROTEIN A-I molecules which are complexed with PHOSPHOLIPIDS. The lipid-poor pre-beta-HDL particles serve as progenitors of HDL3 and then HDL2 after absorption of free cholesterol from cell membranes, cholesterol esterification, and acquisition of apolipoproteins A-II, Cs, and E. Pre-beta-HDL initiate the reverse cholesterol transport process from cells to liver.Bacterial Outer Membrane Proteins: Proteins isolated from the outer membrane of Gram-negative bacteria.Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor.Apolipoprotein E2: One of three major isoforms of apolipoprotein E. In humans, Apo E2 differs from APOLIPOPROTEIN E3 at one residue 158 where arginine is replaced by cysteine (R158--C). In contrast to Apo E3, Apo E2 displays extremely low binding affinity for LDL receptors (RECEPTORS, LDL) which mediate the internalization and catabolism of lipoprotein particles in liver cells. ApoE2 allelic homozygosity is associated with HYPERLIPOPROTEINEMIA TYPE III.Cardiovascular Diseases: Pathological conditions involving the CARDIOVASCULAR SYSTEM including the HEART; the BLOOD VESSELS; or the PERICARDIUM.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.Vitamin E: A generic descriptor for all TOCOPHEROLS and TOCOTRIENOLS that exhibit ALPHA-TOCOPHEROL activity. By virtue of the phenolic hydrogen on the 2H-1-benzopyran-6-ol nucleus, these compounds exhibit varying degree of antioxidant activity, depending on the site and number of methyl groups and the type of ISOPRENOIDS.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.Lysophosphatidylcholines: Derivatives of PHOSPHATIDYLCHOLINES obtained by their partial hydrolysis which removes one of the fatty acid moieties.Iodine Radioisotopes: Unstable isotopes of iodine that decay or disintegrate emitting radiation. I atoms with atomic weights 117-139, except I 127, are radioactive iodine isotopes.Emulsions: Colloids formed by the combination of two immiscible liquids such as oil and water. Lipid-in-water emulsions are usually liquid, like milk or lotion. Water-in-lipid emulsions tend to be creams. The formation of emulsions may be aided by amphiphatic molecules that surround one component of the system to form MICELLES.Receptors, Oxidized LDL: A group of cell-surface receptors for oxidatively modified LOW-DENSITY LIPOPROTEINS. The group includes certain SCAVENGER RECEPTORS that contribute to the pathogenesis of ATHEROSCLEROSIS by uptake of oxidized LDL.Chromatography, Gel: Chromatography on non-ionic gels without regard to the mechanism of solute discrimination.Reference Values: The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.Chemical Precipitation: The formation of a solid in a solution as a result of a chemical reaction or the aggregation of soluble substances into complexes large enough to fall out of solution.Heptanoic Acids: 7-carbon saturated monocarboxylic acids.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.1-Alkyl-2-acetylglycerophosphocholine Esterase: A lipoprotein-associated PHOSPHOLIPASE A2 which modulates the action of PLATELET ACTIVATING FACTOR by hydrolyzing the SN-2 ester bond to yield the biologically inactive lyso-platelet-activating factor. It has specificity for phospholipid substrates with short-chain residues at the SN-2 position, but inactive against long-chain phospholipids. Deficiency in this enzyme is associated with many diseases including ASTHMA, and HYPERCHOLESTEROLEMIA.Molecular Weight: The sum of the weight of all the atoms in a molecule.Endothelium, Vascular: Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.Fatty Acids, Nonesterified: FATTY ACIDS found in the plasma that are complexed with SERUM ALBUMIN for transport. These fatty acids are not in glycerol ester form.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Membrane Proteins: Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.Egg Yolk: Cytoplasm stored in an egg that contains nutritional reserves for the developing embryo. It is rich in polysaccharides, lipids, and proteins.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.alpha-Macroglobulins: Glycoproteins with a molecular weight of approximately 620,000 to 680,000. Precipitation by electrophoresis is in the alpha region. They include alpha 1-macroglobulins and alpha 2-macroglobulins. These proteins exhibit trypsin-, chymotrypsin-, thrombin-, and plasmin-binding activity and function as hormonal transporters.Centrifugation, Density Gradient: Separation of particles according to density by employing a gradient of varying densities. At equilibrium each particle settles in the gradient at a point equal to its density. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Niacin: A water-soluble vitamin of the B complex occurring in various animal and plant tissues. It is required by the body for the formation of coenzymes NAD and NADP. It has PELLAGRA-curative, vasodilating, and antilipemic properties.ATP-Binding Cassette Transporters: A family of MEMBRANE TRANSPORT PROTEINS that require ATP hydrolysis for the transport of substrates across membranes. The protein family derives its name from the ATP-binding domain found on the protein.Blood Glucose: Glucose in blood.Blood Protein DisordersEndocytosis: Cellular uptake of extracellular materials within membrane-limited vacuoles or microvesicles. ENDOSOMES play a central role in endocytosis.Coronary Artery Disease: Pathological processes of CORONARY ARTERIES that may derive from a congenital abnormality, atherosclerotic, or non-atherosclerotic cause.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.Rats, 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. This also includes animals with a long history of closed colony breeding.Homozygote: An individual in which both alleles at a given locus are identical.Scavenger Receptors, Class A: A family of scavenger receptors that mediate the influx of LIPIDS into MACROPHAGES and are involved in FOAM CELL formation.Lipoprotein-X: An abnormal lipoprotein present in large amounts in patients with obstructive liver diseases such as INTRAHEPATIC CHOLESTASIS. LP-X derives from the reflux of BILE lipoproteins into the bloodstream. LP-X is a low-density lipoprotein rich in free CHOLESTEROL and PHOSPHOLIPIDS but poor in TRIGLYCERIDES; CHOLESTEROL ESTERS; and protein.Sterols: Steroids with a hydroxyl group at C-3 and most of the skeleton of cholestane. Additional carbon atoms may be present in the side chain. (IUPAC Steroid Nomenclature, 1987)Lipid Peroxides: Peroxides produced in the presence of a free radical by the oxidation of unsaturated fatty acids in the cell in the presence of molecular oxygen. The formation of lipid peroxides results in the destruction of the original lipid leading to the loss of integrity of the membranes. They therefore cause a variety of toxic effects in vivo and their formation is considered a pathological process in biological systems. Their formation can be inhibited by antioxidants, such as vitamin E, structural separation or low oxygen tension.Simvastatin: A derivative of LOVASTATIN and potent competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL RECEPTORS, it increases breakdown of LDL CHOLESTEROL.Low Density Lipoprotein Receptor-Related Protein-5: LDL-receptor related protein that combines with FRIZZLED RECEPTORS at the cell surface to form receptors that bind WNT PROTEINS. The protein plays an important role in the WNT SIGNALING PATHWAY in OSTEOBLASTS and during EMBRYONIC DEVELOPMENT.Hyperlipoproteinemia Type V: A severe type of hyperlipidemia, sometimes familial, that is characterized by the elevation of both plasma CHYLOMICRONS and TRIGLYCERIDES contained in VERY-LOW-DENSITY LIPOPROTEINS. Type V hyperlipoproteinemia is often associated with DIABETES MELLITUS and is not caused by reduced LIPOPROTEIN LIPASE activity as in HYPERLIPOPROTEINEMIA TYPE I .Bacterial Proteins: Proteins found in any species of bacterium.Copper: A heavy metal trace element with the atomic symbol Cu, atomic number 29, and atomic weight 63.55.Plant Oils: Oils derived from plants or plant products.Immunoelectrophoresis: A technique that combines protein electrophoresis and double immunodiffusion. In this procedure proteins are first separated by gel electrophoresis (usually agarose), then made visible by immunodiffusion of specific antibodies. A distinct elliptical precipitin arc results for each protein detectable by the antisera.Fat Emulsions, Intravenous: Emulsions of fats or lipids used primarily in parenteral feeding.Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate BONE MARROW and released into the BLOOD; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.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.Copper Sulfate: A sulfate salt of copper. It is a potent emetic and is used as an antidote for poisoning by phosphorus. It also can be used to prevent the growth of algae.Insulin: A 51-amino acid pancreatic hormone that plays a major role in the regulation of glucose metabolism, directly by suppressing endogenous glucose production (GLYCOGENOLYSIS; GLUCONEOGENESIS) and indirectly by suppressing GLUCAGON secretion and LIPOLYSIS. Native insulin is a globular protein comprised of a zinc-coordinated hexamer. Each insulin monomer containing two chains, A (21 residues) and B (30 residues), linked by two disulfide bonds. Insulin is used as a drug to control insulin-dependent diabetes mellitus (DIABETES MELLITUS, TYPE 1).Antioxidants: Naturally occurring or synthetic substances that inhibit or retard the oxidation of a substance to which it is added. They counteract the harmful and damaging effects of oxidation in animal tissues.Binding, Competitive: The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.Obesity: A status with BODY WEIGHT that is grossly above the acceptable or desirable weight, usually due to accumulation of excess FATS in the body. The standards may vary with age, sex, genetic or cultural background. In the BODY MASS INDEX, a BMI greater than 30.0 kg/m2 is considered obese, and a BMI greater than 40.0 kg/m2 is considered morbidly obese (MORBID OBESITY).Body Weight: The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms.Diet: Regular course of eating and drinking adopted by a person or animal.Hydroxycholesterols: Cholesterol which is substituted by a hydroxy group in any position.Immunodiffusion: Technique involving the diffusion of antigen or antibody through a semisolid medium, usually agar or agarose gel, with the result being a precipitin reaction.Pravastatin: An antilipemic fungal metabolite isolated from cultures of Nocardia autotrophica. It acts as a competitive inhibitor of HMG CoA reductase (HYDROXYMETHYLGLUTARYL COA REDUCTASES).Xanthomatosis: A condition marked by the development of widespread xanthomas, yellow tumor-like structures filled with lipid deposits. Xanthomas can be found in a variety of tissues including the SKIN; TENDONS; joints of KNEES and ELBOWS. Xanthomatosis is associated with disturbance of LIPID METABOLISM and formation of FOAM CELLS.Body Mass Index: An indicator of body density as determined by the relationship of BODY WEIGHT to BODY HEIGHT. BMI=weight (kg)/height squared (m2). BMI correlates with body fat (ADIPOSE TISSUE). Their relationship varies with age and gender. For adults, BMI falls into these categories: below 18.5 (underweight); 18.5-24.9 (normal); 25.0-29.9 (overweight); 30.0 and above (obese). (National Center for Health Statistics, Centers for Disease Control and Prevention)Pyrroles: Azoles of one NITROGEN and two double bonds that have aromatic chemical properties.Phosphotungstic Acid: Tungsten hydroxide oxide phosphate. A white or slightly yellowish-green, slightly efflorescent crystal or crystalline powder. It is used as a reagent for alkaloids and many other nitrogen bases, for phenols, albumin, peptone, amino acids, uric acid, urea, blood, and carbohydrates. (From Merck Index, 11th ed)Heterozygote: An individual having different alleles at one or more loci regarding a specific character.CHO Cells: CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.Chylomicron Remnants: Metabolic products of chylomicron particles in which TRIGLYCERIDES have been selectively removed by the LIPOPROTEIN LIPASE. These remnants carry dietary lipids in the blood and are cholesterol-rich. Their interactions with MACROPHAGES; ENDOTHELIAL CELLS; and SMOOTH MUSCLE CELLS in the artery wall can lead to ATHEROSCLEROSIS.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Chromatography, Affinity: A chromatographic technique that utilizes the ability of biological molecules to bind to certain ligands specifically and reversibly. It is used in protein biochemistry. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Heparin Lyase: An enzyme of the isomerase class that catalyzes the eliminative cleavage of polysaccharides containing 1,4-linked D-glucuronate or L-iduronate residues and 1,4-alpha-linked 2-sulfoamino-2-deoxy-6-sulfo-D-glucose residues to give oligosaccharides with terminal 4-deoxy-alpha-D-gluc-4-enuronosyl groups at their non-reducing ends. (From Enzyme Nomenclature, 1992) EC 4.2.2.7.Diabetes Mellitus, Type 2: A subclass of DIABETES MELLITUS that is not INSULIN-responsive or dependent (NIDDM). It is characterized initially by INSULIN RESISTANCE and HYPERINSULINEMIA; and eventually by GLUCOSE INTOLERANCE; HYPERGLYCEMIA; and overt diabetes. Type II diabetes mellitus is no longer considered a disease exclusively found in adults. Patients seldom develop KETOSIS but often exhibit OBESITY.AzetidinesThiobarbituric Acid Reactive Substances: Low-molecular-weight end products, probably malondialdehyde, that are formed during the decomposition of lipid peroxidation products. These compounds react with thiobarbituric acid to form a fluorescent red adduct.Macrophages, Peritoneal: Mononuclear phagocytes derived from bone marrow precursors but resident in the peritoneum.Low Density Lipoprotein Receptor-Related Protein-6: An LDL-receptor related protein that combines with cell surface FRIZZLED RECEPTORS to form WNT PROTEIN-binding receptors. The protein plays an important role in the WNT SIGNALING PATHWAY during EMBRYONIC DEVELOPMENT and in regulation of vascular cell proliferation.Hypobetalipoproteinemias: Conditions with abnormally low levels of BETA-LIPOPROTEINS (low density lipoproteins or LDL) in the blood. It is defined as LDL values equal to or less than the 5th percentile for the population. They include the autosomal dominant form involving mutation of the APOLIPOPROTEINS B gene, and the autosomal recessive form involving mutation of the microsomal triglyceride transfer protein. All are characterized by low LDL and dietary fat malabsorption.Fenofibrate: An antilipemic agent which reduces both CHOLESTEROL and TRIGLYCERIDES in the blood.Metabolic Syndrome X: A cluster of metabolic risk factors for CARDIOVASCULAR DISEASES and TYPE 2 DIABETES MELLITUS. The major components of metabolic syndrome X include excess ABDOMINAL FAT; atherogenic DYSLIPIDEMIA; HYPERTENSION; HYPERGLYCEMIA; INSULIN RESISTANCE; a proinflammatory state; and a prothrombotic (THROMBOSIS) state. (from AHA/NHLBI/ADA Conference Proceedings, Circulation 2004; 109:551-556)
  • So Forte and Nikanjamundertook to develop synthetic, nano-sized LDL particles (nLDLs), much smaller in size than natural LDLs and easier to work with, which would target the low density lipoprotein receptors on glioblastoma multiforme cells. (lbl.gov)
  • Measurements of cholesterol concentrations eluted from the FPLC fractions and Coomassie staining of plasma lipoproteins were performed as described ( 16 ). (pnas.org)
  • Since PCSK9 is a protease that breaks down the LDL receptor, itself the major clearance mechanism for cholesterol from the blood, blocking PCSK9 increases the level of LDL receptor and therefore dramatically reduces circulating cholesterol, and in particular the triglyceride-rich lipoproteins, such as LDL, that are implicated in causing cardiovascular disease. (forbes.com)
  • Anti-PCSK9 antibodies are the jewel in the crown of modern genomic medicine, illustrating what many hope will be a paradigm for future drug discovery. (forbes.com)
  • The additional low-density lipoprotein cholesterol lowering obtained with PCSK9 inhibition will be able to reduce the additional risk, but its effect on cardiovascular events has to be evaluated in future studies. (dovepress.com)
  • Proprotein convertase subtilisin kexin type 9 (PCSK9) is a major player in cholesterol regulation - mutations in this gene can lead to familial hypercholesterolemia, a genetic disorder characterized by abnormally high cholesterol levels and cardiovascular disease. (asbmb.org)
  • While a number of these loci harbor gene targets of currently approved therapies, such as statins and PCSK9 inhibitors, the majority of the annotated genes at these loci encode for proteins involved in vessel wall function with no known drugs available. (frontiersin.org)
  • Recently it was revealed that the secreted Proprotein Convertase Subtilisin Kexin 9 (PCSK9) binds with LDL-receptor (LDL-R) causing its degradation in the lysosome with the result of LDL-C accumulating in the blood. (sigmaaldrich.com)
  • Repatha is an investigational fully human monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein that reduces the liver's ability to remove low-density lipoprotein cholesterol (LDL-C), or "bad" cholesterol, from the blood. (amgen.com)
  • His lab showed that PCSK9 was capable of destroying the LDL receptor, which clears LDL from the bloodstream. (rockefeller.edu)
  • Paris and Tarrytown, NY - September 12, 2018 - Sanofi and Regeneron Pharmaceuticals, Inc. announced that the U.S. Food and Drug Administration (FDA) has accepted a supplemental Biologics License Application (sBLA) for Praluent ® (alirocumab) Injection, a PCSK9 inhibitor. (yahoo.com)
  • Praluent inhibits the binding of PCSK9 (proprotein convertase subtilisin/kexin type 9) to the LDL receptor and thereby increases the number of available LDL receptors on the surface of liver cells to clear LDL, which lowers LDL-C levels in the blood. (yahoo.com)
  • These mutations were either in the gene encoding the low density lipoprotein receptor-related protein-5 ( LRP5 ) or in a gene ( SOST ) encoding a protein (Sclerostin) that potentially binds and regulates the function of LRP5 and its family members LRP4 and LRP6. (hindawi.com)
  • Part one hour of therapy, this virus receptor complex then binds to patienthencounter. (roanokechowan.edu)
  • Lomitapide is a selective inhibitor of microsomal transfer protein (MTP), which is involved in the assembly of lipoproteins that ultimately build LDL levels in HoFH patients. (biomedreports.com)
  • One such example was the body of work that resulted in the identification of the Low Density Lipoprotein-Related Protein (LRP5) as a key regulator of bone mass. (hindawi.com)
  • LPA stimulates three G protein-linked, plasma membrane-associated receptors [LPA 1 , LPA 2 , and LPA 3 , formerly edg2, edg4, and edg7 ( 6 )] that recognize extracellular LPA ( 7 ). (pnas.org)
  • Understanding HLA-peptide binding is essential for the development of vaccines and protein therapies, the identification of methods to prevent autoimmune diseases and the prediction of adverse drug reactions. (ualr.edu)
  • Since the HLAs and peptides are two core components to trigger immunologic responses, the complete Class I HLA-binding peptidome accomplished in this study provides the scientific community a rich source for understanding the interactions between Class I HLAs and peptides, potentially assisting in the development of vaccines and protein therapeutics, facilitating studies of autoimmune diseases and improving the prediction of drug adverse reactions. (ualr.edu)
  • This protein plays a major regulatory role in cholesterol homeostasis. (news-medical.net)
  • Previous studies showed that knockdown of ITSN-1s (KD ITSN ), an endocytic protein involved in regulating lung vascular permeability and endothelial cells (ECs) survival, induced apoptotic cell death, a major obstacle in developing a cell culture system with prolonged ITSN-1s inhibition 1 . (jove.com)
  • This protein is also a component of other multisubunit complexes e.g. thyroid hormone receptor-(TR-) associated proteins which interact with TR and facilitate TR function on DNA templates in conjunction with initiation factors and cofactors. (nih.gov)
  • One of the major pathological hallmarks of the disease are amyloid plaques, composed primarly of insoluble fibrils of Aβ peptide: this molecule derives from the processing of the transmembrane amyloid precursor protein (APP) by different secretases and its production is a physiological event, but the anormal increase in Aβ levels appears to be toxic both in vitro and in vivo. (eurekaselect.com)
  • 2015. Protein Kinase C is involved in the induction of ATP-Binding cassette transporter A1 expression by liver X receptor/retinoid X receptor agonist in human macrophages . (cardiff.ac.uk)
  • this corresponds to harrison stage fales in x laevis and at receptor mrna localized to the external growth factors and signaling protein rgs dei nes a major determinant of morphogenesis is intimately intertwined with the exponential growth in the genitourinary tract and the nephric mesoderm cells are likely to injure the minor calyces and collecting. (nationalnewstoday.com)
  • Individuals with natural mutations in PCSK-9 have less heart disease, and this is what prompted development of drugs to target this particular protein. (yu.edu)
  • Certain ligand-activated nuclear receptors provide promising new targets for this purpose. (ahajournals.org)
  • Nuclear receptors are transcription factors that, on ligand binding by specific molecules and cofactor recruitment, regulate the expression of specific target genes. (ahajournals.org)
  • The peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that belong to the superfamily of nuclear hormone receptors and play an important role in nutrient homeostasis [ 1 - 3 ]. (hindawi.com)
  • Modified Citrus Pectin (MCP) acts as a ligand for galectin-3, which plays a major role in tumor formation and progression (7) (8) . (mskcc.org)
  • LPA also is generated during platelet activation ( 5 ) to become a major growth factor of serum. (pnas.org)
  • The high concentration of selenium in the Brazil nut may improve serum lipoprotein, due to its stimulation of the metabolically active form of thyroid hormones. (biomedcentral.com)
  • The present study investigated the effects of a healthy diet associated with defatted Brazil nut flour on thyroid hormones and in serum lipoproteins in dyslipidemic and hypertensive patients. (biomedcentral.com)
  • We showed the Class I HLA-binding peptidome could significantly improve prediction of adverse drug reactions through binding to Class I HLA using molecular docking. (ualr.edu)
  • FDA and EMA guidance documents indicate that for clinical approval of new drugs for the treatment of NASH, trials should include patients who have significantly higher risk of progression to cirrhosis and hepatic decompensation, as defined as those who have biopsy-proven NASH with stage 2 fibrosis or higher. (bmj.com)
  • Nuclear companies outside Mexico City, while significantly receptors same as anabolic steroids. (3riversstadium.com)
  • Although many have pointed out the tiny pool of patients that Aegerion and competitor ISIS will be fighting over, Aegerion has the luxury of commercializing the most efficacious drug in the indication (based on clinical trial data). (biomedreports.com)
  • Most enteric bacteria, as to patients with zinc oxide, but only be complicated by v2-receptors. (diarimaresme.com)
  • EGFR receptor modulators and green, thereby coun- ters these patients at work load of hypertension. (diarimaresme.com)
  • Conceptually, several major problems may exist in the anti-endotoxin strategies employed to date, none of which have used a diagnostic assay to identify patients who might benefit from anti-LPS target-directed therapy. (biomedcentral.com)
  • In impotent patients suggests that are negative inotropic drugs that hepatic conjugation figure, and breast-feeding. (imagenenaccion.org)
  • STEMI patients benefit, including pulsed doses of about the colon motility through- out the same drug resistance. (imagenenaccion.org)
  • We used publicly available data reporting major adverse CV events (MACE) rates from other cohorts of HoFH patients to compare event rates for an equivalent number of patient years of exposure (98) in the lomitapide extension trial (NCT00943306). (biomedcentral.com)
  • There were fewer major CV events per 1000 patient months of treatment in patients taking lomitapide, mipomersen or evolocumab than reported in the mipomersen cohort prior to starting mipomersen. (biomedcentral.com)
  • Patients with haematological effects are susceptible, which is the drug treat- ing. (st-systemtronic.com)
  • Doxazosin improves symptoms of patients with crohn's leukotriene receptor Erythromycin inhibits cYP3A The disorder. (st-systemtronic.com)
  • Patients with type 2 diabetes have increased cancer risk, although the risk association of cancer with antidiabetes drugs remains controversial ( 1 ). (diabetesjournals.org)
  • In support of these findings, epidemiological studies have reported reduced cancer risk ( 9 ) and associated mortality ( 10 ) in type 2 diabetic patients treated with metformin compared with other antidiabetes drugs. (diabetesjournals.org)
  • The primary lesion in some patients is known to occur in the cells' initial handling of the major cholesterol-carrying lipoprotein of plasma. (elsevier.com)
  • Stretch receptors on the main effects of polyuria, obesity in patients a remediable and hypertriglyceridaemia. (freejobaware.com)
  • In patients with immunophilins and their absorption, reducing absorp- tion of h1-receptors. (freejobaware.com)
  • These drugs usually come with written directions for patients and should be used only as directed by the prescribing physician. (encyclopedia.com)
  • The Patients suffered from various factors and cholesterol is one of the major sources of diseases. (scribd.com)
  • The FDA ordered that "black box" warnings should be on the most widely prescribed drugs, and that patients should receive medication guideline material. (pharmacytimes.com)
  • 6. Lipoprotein is a huge advance from the left parotid gland and may enhance the patients conditions (eg, carotid disease, renal dysfunction, or cirrhosis of the patient, restoring chest wall compliance and adherence. (suagm.edu)
  • Two major trials are still ongoing: FOURIER (evolocumab, 27,000 patients) and ODYSSEY OUTCOMES (alirocumab, 18,000 patients), with Montefiore actively enrolling patients in the latter. (yu.edu)
  • The drugs are projected to cost between five and ten thousand dollars-or more-annually per patient and will likely be accessible only to a subset of high-risk patients, at least initially. (yu.edu)
  • Whether insurance companies will willingly pay for these drugs for a wider group of patients remains to be seen. (yu.edu)
  • Still, due to the efficacy of these drugs as shown in trials, and their low side-effect profile, they are eagerly awaited by doctors who treat those with heart disease and their patients. (yu.edu)
  • The major intracellular nucleoside reverse transcriptase from poisons and various vitamin d. (imagenenaccion.org)
  • These data suggested that codelivery of anti-miR21 and chemotherapeutic agents by HMNs might be a promising strategy for antitumor therapy, and could restore the drug sensitivity of cancer cells, alter intracellular drug distribution, and ultimately enhance chemotherapeutic effects. (dovepress.com)
  • My wife and for the current such as blatant gynaecomastia, severe steroid acne behaviour and alteration of the intracellular translocation of calcium via the ryanodine receptor. (3riversstadium.com)
  • The Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily and has emerged as a key player in the control of multiple metabolic pathways. (ahajournals.org)
  • Ananthanarayanan M, Balasubramanian N, Makishima M, Mangelsdorf DJ, Suchy FJ (2001) Human bile salt export pump promoter is transactivated by the farnesoid X receptor/bile acid receptor. (springer.com)
  • A 2018 British analysis of 10 studies involving more than 77,000 participants revealed that taking Omega-3 supplements for an average of four years "had no significant association with reductions in fatal or nonfatal coronary heart disease or any major vascular events. (mnn.com)
  • But generally, studies looking at diabetes drugs have not shown a benefit on larger-scale complications such as coronary disease or heart failure. (medpagetoday.com)
  • Familial hypercholesterolemia, a widespread human genetic disorder implicated in vascular and coronary disease, has had no laboratory animal counterpart that would enable the pathogenesis to be analyzed and drugs to be tested in vivo. (elsevier.com)
  • The major side effect of stimulating the cartilage matrix and inhibiting dna methyltransferase, which causes a mild to moderate chronic obstructive pulmonary disease copd, coronary artery disease and the potential advantages of hfy, no significant long term treatment of the potential. (roanokechowan.edu)
  • changes Are compared for story of coronary receptor plaque been for the pathology of Maximum arteries. (sixpersimmons.com)
  • These trials have shown that these drugs lower LDL cholesterol by more than 50 percent, and the data preliminarily suggest that they reduce heart attack and acute coronary syndromes and save lives. (yu.edu)
  • After a seemingly unstoppable rally since the US launch of HoFH (Homozygous familial hypercholesterolemia) drug Juxtapid (lomitapide), Aegerion Pharmaceuticals (NASDAQ: AEGR) finally "cooled off" to some extent, although it's worth noting that the CHMP decision contained very positive commentary regarding the drug's efficacy in the treatment of high cholesterol. (biomedreports.com)
  • We have now identified LDL receptors on glioblastoma multiforme tumor cells that can serve as specific molecular targets,' says Trudy Forte, a specialist in lipoprotein research with joint appointments in Berkeley Lab's Life Sciences Division and CHORI. (lbl.gov)
  • Because these LDL receptors are sparse in normal human brain tissue but elevated on the tumor cells, our synthetic nano-LDLs can deliver drugs to the glioblastoma multiforme tumors while sparing healthy cells. (lbl.gov)
  • Tumor cells generally have high cholesterol requirements as they are rapidly dividing, and LDLs are the major transporters of cholesterol in the plasma,' explained Forte. (lbl.gov)
  • Furthermore, the codelivery of anti-miR21 and NLS-Dox by HMNs showed synergistic antiproliferative effects in MCF7/ADR-bearing nude mice, and was more effective in tumor inhibition than other drug formulations. (dovepress.com)
  • This requires first learning whether the tumor stem cells in culture express LDL receptors, and next establishing a selection or screening procedure to identify receptor-deficient mutants in mutagenized cell cultures. (elsevier.com)
  • Attinkara R, Mwinyi J, Truninger K, Regula J, Gaj P, Rogler G et al (2012) Association of genetic variation in the NR1H4 gene, encoding the nuclear bile acid receptor FXR, with inflammatory bowel disease. (springer.com)
  • A specific pediatric study within the project focused on a lifestyle intervention on overweight children with variations in the melanocortin 4 receptor gene. (europa.eu)
  • These drug therapy, a maximum activity, a lower-affinity/higher- capacity of where to buy dostinex in uk common of the heart block the disease. (diarimaresme.com)
  • In order to improve the bioavailability and reduce the toxic and side effects, brain targeting of amaryllidaceous alkaloids was enhanced by considering low density lipoprotein (LDL) receptors of blood-brain barrier (BBB) endothelial cells as therapeutic targets. (deepdyve.com)
  • The argument is often made that the sheer volume of bio-data being discovered and the sophistication of the bio-informatics tools used to uncover relationships within it will inevitably lead over the years to the identification of a vast array of new drug targets. (ddw-online.com)
  • Curr Drug Targets. (mcmaster.ca)
  • In this mini-review, we highlight the most recently identified loci that have predicted roles in the vessel wall and provide genetic context for pre-existing therapies as well as new drug targets informed from GWAS. (frontiersin.org)
  • Clonidine is a blood pressure drug that targets the a2 adrenergic receptor. (blogspot.com)
  • This can not only improve the efficacy of the drug but also decrease systemic and/or unwanted tissue/organ-specific toxicity (T). Development of a prodrug with improved properties may also represent a life-cycle management opportunity. (aspetjournals.org)