Cholesterol Ester Transfer Protein
Cholesteryl ester transfer protein (CETP), also called plasma lipid transfer protein, is a plasma protein that facilitates the transport of cholesteryl esters and triglycerides between the lipoproteins. It collects triglycerides from very-low-density (VLDL) or Chylomicrons and exchanges them for cholesteryl esters from high-density lipoproteins (HDL), and vice versa. Most of the time, however, CETP does a heteroexchange, trading a triglyceride for a cholesteryl ester or a cholesteryl ester for a triglyceride. Genetics The ''CETP'' gene is located on the sixteenth chromosome (16q21). Protein Fold The crystal structure of CETP is that of dimer of two TUbular LIPid (TULIP) binding domains. Each domain consists of a core of 6 elements: 4 beta-sheets forming an extended superhelix; 2 flanking elements that tend to include some alpha helix. The sheets wrap around the helices to produce a cylinder 6 x 2.5 x 2.5 nm. CETP contains two of these domains that interact head-to-head ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Blood Plasma
Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the intravascular part of extracellular fluid (all body fluid outside cells). It is mostly water (up to 95% by volume), and contains important dissolved proteins (6–8%; e.g., serum albumins, globulins, and fibrinogen), glucose, clotting factors, electrolytes (, , , , , etc.), hormones, carbon dioxide (plasma being the main medium for excretory product transportation), and oxygen. It plays a vital role in an intravascular osmotic effect that keeps electrolyte concentration balanced and protects the body from infection and other blood-related disorders. Blood plasma is separated from the blood by spinning a vessel of fresh blood containing an anticoagulant in a centrifuge until the blood cells fall to the bottom of the tube. The blood plasma is t ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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BPIFA3
BPI fold containing family A, member 3 is a protein that in humans is encoded by the ''BPIFA3'' gene. The gene is also known as ''SPLUNC3 and C20orf71'' in humans and the orthologous gene in mice is ''1700058C13Rik''. Model organisms Model organisms have been used in the study of BPIFA3 function. A conditional knockout mouse line, called ''1700058C13Riktm1a(KOMP)Wtsi'' was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty three tests were carried out on mutant In biology, and especially in genetics, a mutant is an organism or a new genetic character arising or resulting from an instance of mutation, which is generally an alteration of the DNA sequence of the genome or chromosom ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Torcetrapib
Torcetrapib (CP-529,414, Pfizer) was a drug being developed to treat hypercholesterolemia (elevated cholesterol levels) and prevent cardiovascular disease. Its development was halted in 2006 when phase III studies showed excessive all-cause mortality in the treatment group receiving a combination of atorvastatin (Lipitor) and torcetrapib. Medical uses Torcetrapib has not been found to reduce either cardiovascular disease or risk of death in those already taking a statin drug. Mechanism Torcetrapib acts (as a CETP inhibitor) by inhibiting cholesterylester transfer protein (CETP), which normally transfers cholesterol from HDL cholesterol to very low density or low density lipoproteins (VLDL or LDL). Inhibition of this process results in higher HDL cholesterol levels and reduces LDL cholesterol levels. According to Harvard Heart Letter: "HDL cholesterol is turning out to be a much more complex substance than we once believed. Instead of a single kind of particle, HDL cholestero ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Metabolic Syndrome
Metabolic syndrome is a clustering of at least three of the following five medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL). Metabolic syndrome is associated with the risk of developing cardiovascular disease and type 2 diabetes. In the U.S., about 25% of the adult population has metabolic syndrome, a proportion increasing with age, particularly among racial and ethnic minorities. Insulin resistance, metabolic syndrome, and prediabetes are closely related to one another and have overlapping aspects. The syndrome is thought to be caused by an underlying disorder of energy utilization and storage. The cause of the syndrome is an area of ongoing medical research. Signs and symptoms The key sign of metabolic syndrome is central obesity, also known as visceral, male-pattern or apple-shaped adiposity. It is characterized by adipose tissue accumulation predominantly around the wais ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Cardiovascular Disease
Cardiovascular disease (CVD) is a class of diseases that involve the heart or blood vessels. CVD includes coronary artery diseases (CAD) such as angina and myocardial infarction (commonly known as a heart attack). Other CVDs include stroke, heart failure, hypertensive heart disease, rheumatic heart disease, cardiomyopathy, abnormal heart rhythms, congenital heart disease, valvular heart disease, carditis, aortic aneurysms, peripheral artery disease, thromboembolic disease, and venous thrombosis. The underlying mechanisms vary depending on the disease. It is estimated that dietary risk factors are associated with 53% of CVD deaths. Coronary artery disease, stroke, and peripheral artery disease involve atherosclerosis. This may be caused by high blood pressure, smoking, diabetes mellitus, lack of exercise, obesity, high blood cholesterol, poor diet, excessive alcohol consumption, and poor sleep, among other things. High blood pressure is estimated to account for approximat ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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High-density Lipoprotein
High-density lipoprotein (HDL) is one of the five major groups of lipoproteins. Lipoproteins are complex particles composed of multiple proteins which transport all fat molecules (lipids) around the body within the water outside cells. They are typically composed of 80–100 proteins per particle (organized by one, two or three ApoA. HDL particles enlarge while circulating in the blood, aggregating more fat molecules) and transporting up to hundreds of fat molecules per particle. Overview Lipoproteins are divided into five subgroups, by density/size (an inverse relationship), which also correlates with function and incidence of cardiovascular events. Unlike the larger lipoprotein particles, which deliver fat molecules to cells, HDL particles remove fat molecules from cells. The lipids carried include cholesterol, phospholipids, and triglycerides, amounts of each are variable. Increasing concentrations of HDL particles are associated with decreasing accumulation of atherosclerosis ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Trans Fat
Trans fat, also called trans-unsaturated fatty acids, or trans fatty acids, is a type of unsaturated fat that naturally occurs in small amounts in meat and milk fat. It became widely produced as an unintentional byproduct in the industrial processing of vegetable and fish oils in the early 20th century for use in margarine and later also in snack food, packaged baked goods, and for frying fast food. In nature, unsaturated fatty acids generally have ''cis'' configurations as opposed to ''trans'' configurations. While saturated fatty acids without any double bonds are created from unsaturated fats by the process of fat hydrogenation, partial hydrogenation converts some of the ''cis'' double bonds into ''trans'' double bonds by an isomerization reaction with the catalyst used for the hydrogenation, which yields a trans fat. In food production, liquid cis-unsaturated fats such as vegetable oils are hydrogenated to produce saturated fats, which have more desirable physical prop ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Elaidic Acid
Elaidic acid is a chemical compound with the formula , specifically the fatty acid with structural formula HO(O=)C–(CH2–)7CH=CH–(CH2–)8H, with the double bond (between carbon atoms 9 and 10) in ''trans'' configuration. It is a colorless oily solid. Its salts and esters are called elaidates. Elaidic acid is an unsaturated trans fatty acid, with code C18:1 ''trans''-9. This compound has attracted attention because it is a major trans fat found in hydrogenated vegetable oils, and trans fats have been implicated in heart disease. It is the trans isomer of oleic acid. The name of the elaidinization reaction comes from elaidic acid. Its name comes from the Ancient Greek word ἔλαιον (''elaion''), meaning oil. Occurrence and bioactivity Elaidic acid occurs naturally in small amounts in caprine and bovine milk (very roughly 0.1% of the fatty acids) and in some meats. Elaidic acid increases plasma cholesterylester transfer protein (CETP) activity which lowers HDL ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Hypertriglyceridemia
Hypertriglyceridemia is the presence of high amounts of triglycerides in the blood. Triglycerides are the most abundant fatty molecule in most organisms. Hypertriglyceridemia occurs in various physiologic conditions and in various diseases, and high triglyceride levels are associated with atherosclerosis, even in the absence of hypercholesterolemia (high cholesterol levels) and predispose to cardiovascular disease. Chronically elevated serum triglyceride levels are a component of metabolic syndrome and Non-alcoholic fatty liver disease (NAFLD), both of which typically involve obesity and contribute significantly to cardiovascular mortality in industrialised countries as of 2021. Extreme triglyceride levels also increase the risk of acute pancreatitis. Hypertriglyceridemia itself is usually symptomless, although high levels may be associated with skin lesions known as ''xanthomas''. Signs and symptoms Most people with elevated triglycerides experience no symptoms. Some forms o ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Coronary Heart Disease
Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the heart muscle due to build-up of atherosclerotic plaque in the arteries of the heart. It is the most common of the cardiovascular diseases. Types include stable angina, unstable angina, myocardial infarction, and sudden cardiac death. A common symptom is chest pain or discomfort which may travel into the shoulder, arm, back, neck, or jaw. Occasionally it may feel like heartburn. Usually symptoms occur with exercise or emotional stress, last less than a few minutes, and improve with rest. Shortness of breath may also occur and sometimes no symptoms are present. In many cases, the first sign is a heart attack. Other complications include heart failure or an abnormal heartbeat. Risk factors include high blood pressure, smoking, diabetes, lack of exercise, obesity, high blood cholesterol, ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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Atherosclerosis
Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheroma, atheromatous plaque. At onset there are usually no symptoms, but if they develop, symptoms generally begin around middle age. When severe, it can result in coronary artery disease, stroke, peripheral artery disease, or kidney problems, depending on which Artery, arteries are affected. The exact cause is not known and is proposed to be multifactorial. Risk factors include dyslipidemia, abnormal cholesterol levels, elevated levels of inflammatory markers, high blood pressure, diabetes, smoking, obesity, family history, genetic, and an unhealthy diet. Atheroma, Plaque is made up of fat, cholesterol, calcium, and other substances found in the blood. The narrowing of Artery, arteries limits the flow of oxygen-rich blood to parts of the body. Diagnosis is based upon a physical exam, ele ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |
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CETP Inhibitors
A CETP inhibitor is a member of a class of drugs that inhibit cholesterylester transfer protein (CETP). They are intended to reduce the risk of atherosclerosis (a cardiovascular disease) by improving blood lipid levels. At least three medications within this class have failed to demonstrate a beneficial effect. Types These drugs have generally failed in clinical trials, either causing a marked increase in deaths (torcetrapib), or having no meaningful clinical improvement despite HDL increases (dalcetrapib, evacetrapib). Failed: * Torcetrapib, failed in 2006 due to excess deaths in Phase III clinical trials. * Dalcetrapib, development halted in May 2012 when Phase III trials failed to show clinically meaningful efficacy. * Evacetrapib, development discontinued in 2015 due to insufficient efficacy. * Obicetrapib (TA-8995, AMG-899), Phase II results reported in 2015, discontinued in 2017 Succeeded: * Anacetrapib. In 2017, the REVEAL trial based on more than 30,000 participants sh ... [...More Info...]       [...Related Items...]     OR:     [Wikipedia]   [Google]   [Baidu]   |