"Lipid-lowering agent Hypolipidemic agents, or antihyperlipidemic agents, are a diverse group of pharmaceuticals that are used in the treatment of high levels of fats (lipids), such as cholesterol, in the blood (hyperlipidemia). They are called lipid-lowering drugs. There are several classes of hypolipidemic drugs. They may differ in both their impact on the cholesterol profile and adverse effects. For example, some may lower the ""bad cholesterol"" low density lipoprotein (LDL) more so than others, while others may preferentially increase high density lipoprotein (HDL), ""the good cholesterol"". Clinically, the choice of an agent will depend on the patient's cholesterol profile, cardiovascular"
"Low-density lipoprotein Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein which transport all fat molecules around the body in the extracellular water. These groups, from least dense, compared to surrounding water (largest particles) to most dense (smallest particles), are chylomicrons (aka ULDL by the overall density naming convention), very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein and high-density lipoprotein (HDL). LDL delivers fat molecules to the cells and can drive the progression of atherosclerosis if they become oxidized within the walls of arteries. Lipoproteins transfer lipids (fats) around the body in the extracellular fluid, making"
"are not conclusive. Low-density lipoprotein Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein which transport all fat molecules around the body in the extracellular water. These groups, from least dense, compared to surrounding water (largest particles) to most dense (smallest particles), are chylomicrons (aka ULDL by the overall density naming convention), very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), low-density lipoprotein and high-density lipoprotein (HDL). LDL delivers fat molecules to the cells and can drive the progression of atherosclerosis if they become oxidized within the walls of arteries. Lipoproteins transfer lipids (fats) around the body in the"
"ULDL Ultra Low Density Lipoproteins (ULDL), historically commonly called chylomicrons (dating to before these particles were better characterized and understood) are one of the five major groups of lipoprotein, as divided by density or size [an inherently inverse relationship because the larger particles (higher ratio of fat molecules inside compared with the outer emulsifying protein molecules in the shell) and fats are always lower density than either protein or water molecules, i.e. fats float in water.]. Specifically they are the largest and only lipoprotein particles (which transport fat molecules around the body in the water outside cells) which can sometimes"
"plasma lipoprotein particles classified as HDL, LDL, IDL, VLDL and ULDL (a.k.a. chylomicrons) lipoproteins, according to density / size (an inverse relationship), compared with the surrounding plasma water. These complex protein capsules enable fats to be carried in all extracellular water, including the blood stream (an example of emulsification), subgroups of which are primary drivers / modulators of atherosclerosis, the transmembrane proteins of mitochondrion, chloroplast, and bacterial lipoproteins. Proteolipids are a different kind of protein-lipid combination that are insoluble in water. Proteolipids are abundant in brain tissue, and are also present in many other animal and plant tissues. The lipids"
"that has been shown to have beneficial anti-inflammatory properties), and an increase in Serum amyloid A. This altered composition of HDL is commonly referred to as acute-phase HDL in an acute-phase inflammatory response, during which time HDL can lose its ability to inhibit the oxidation of LDL. In fact, this altered composition of HDL is associated with increased mortality and worse clinical outcomes in patients with sepsis. Lipoproteins may be classified as five major groups follows, listed from larger and less dense to smaller and denser. Lipoproteins are larger and less dense when the fat to protein ratio is increased."
"for primary or secondary prevention of cardiovascular disease. Though it has not yet been FDA-approved, the PPAR modulator (sometimes referred to as a SARM) GW501516, currently a research chemical (not for human consumption), has shown a positive effect on HDL-C and an antiatherogenic where LDL is an issue. High-density lipoprotein HDL particles have long been divided into 5 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 which need to export fat molecules. The lipids"
"relevance to human phenotypes. The G1 is a pair of two non-synonymous single nucleotide polymorphisms (SNPs) in almost complete linkage disequilibrium. G2 is an in-frame deletion of the two amino acid residues, N388 and Y389. Apolipoprotein L1 (apoL1) is a minor apoprotein component of HDL (High-density lipoprotein) or 'good cholesterol' which is synthesized in the liver and also in many other tissues, including pancreas, kidney, and brain. APOL1 is found in vascular endothelium, liver, heart, lung, placenta, podocytes, proximal tubules, and arterial cells. The protein has a secreted form that allows it to circulate in the blood. It forms a"
"(if large enough, at close to about 1,000 microns or more) be seen using only a light microscope, at maximum magnification. All the other classes are submicroscopic, one of the reasons these particles were long difficult to identify and better understand. ULDL Ultra Low Density Lipoproteins (ULDL), historically commonly called chylomicrons (dating to before these particles were better characterized and understood) are one of the five major groups of lipoprotein, as divided by density or size [an inherently inverse relationship because the larger particles (higher ratio of fat molecules inside compared with the outer emulsifying protein molecules in the shell)"
"Lipoprotein such as HDL. When HDL takes up free fatty acids from cells to prevent plaque build-up, it begins to increase its overall negative charge and instead stimulates HL to catalysis the triacylglycerides inside of VLDL (very low density lipoprotein). This is because the build-up of negative charge in HDL inhibits binding, but will allow HL to catalyze other lipoproteins. Other lipoproteins, such as ApoE, works in a similar way by inhibiting binding of HL and HDL but will allow HL to catalyze other lipoproteins. Other factors that contribute the regulation of HL are due to sex differences between women"
"glutamine, which are associated with high and low enzymatic activity respectively. The development of atherosclerosis is a complex process, though the main underlying feature is simply an increase in low-density lipoprotein (LDL) oxidation. PON1 and PON3 prevent the formation of atherogenic oxidised-LDL, the form of LDL present in foam cells of an atheromatous plaque. Because of their know association with high-density lipoprotein (HDL) and their effect on oxidized-LDL, PON1 and PON3 are implicated in lowering the risk of developing coronary artery disease and atherosclerosis. PON was identified as an enzyme having organophosphates as its substrates. Reports of the geographic differences"
"under normal, stable physiological conditions, HDL has been shown to be beneficial in a number of ways. LDL contains apolipoprotein B (apoB), which allows LDL to bind to different tissues, such as the artery wall. Once bound, LDL can undergo Beta oxidation, and this can cause a harmful inflammatory response in the body. Normal functioning HDL is able to prevent the process of oxidation of LDL and the subsequent inflammatory processes seen after oxidation. Lipopolysaccharide, or LPS, is the major pathogenic factor on the cell wall of Gram-negative bacteria. Gram-positive bacteria has a similar component named Lipoteichoic acid, or LTA."
"LDL receptor and its impact on lipoprotein metabolism. Familial hypercholesterolemia Familial hypercholesterolemia (FH) is a genetic disorder characterized by high cholesterol levels, specifically very high levels of low-density lipoprotein (LDL, ""bad cholesterol""), in the blood and early cardiovascular disease. Since the underlying body biochemistry is slightly different in individuals with FH , their high cholesterol levels are less responsive to the kinds of cholesterol control methods which are usually more effective in people without FH (such as dietary modification and statin tablets). Nevertheless, treatment (including higher statin doses) is usually effective. FH is classified as a type 2 familial dyslipidemia."
"with high LDL. A second approach would be to discourage the oxidation of LDL, thereby breaking the inflammatory cycle. Lipoproteins consist of a packaging of triglycerides and esterfied cholesterol within a monolayer shell consisting of phospholipids and a class of proteins called apolipoproteins. The phospholipds are amphipathic, consisting of a hydrophobic tail which faces inwards, binding with the triglycerides and cholesterol, and a hydrophilic head which faces outwards, making the lipoproteins water-soluble. Polyunsaturated fatty acids (PUFA) contained in the outer shell make the lipoproteins especially susceptible to oxidation. However, lipoproteins also contain antioxidants which protect the components, vitamin E and"
"HDL has the ability to bind LPS and LTA, creating HDL-LPS complexes to neutralize the harmful effects in the body and clear the LPS from the body. HDL also has significant roles interacting with cells of the immune system to modulate the availability of cholesterol and modulate the immune response itself. Under certain abnormal physiological conditions such as system infection or sepsis, the major components of HDL become altered, The composition and quantity of lipids and apolipoproteins are altered as compared to normal physiological conditions, such as a decrease in HDL cholesterol (HDL-C), phospholipids, apoA-I (a major lipoprotein in HDL"
"including subtypes), and each are classified from both the altered lipid profile and by the genetic abnormality. For example, high LDL (often due to LDL receptor defect) is type 2. Others include defects in chylomicron metabolism, triglyceride metabolism, and metabolism of other cholesterol-containing particles, such as VLDL and IDL. About 1 in 300 to 500 people have mutations in the ""LDLR"" gene that encodes the LDL receptor protein, which normally removes LDL from the circulation, or apolipoprotein B (ApoB), which is the part of LDL that binds with the receptor; mutations in other genes are rare. People who have one"
"taken up from the plaque by SR-B1 receptors, which convert HDL3 to HDL2 which contains higher concentrations of free fatty acids. HDL2 can then interact with LDL and IDL by transferring over fatty acids that have accumulated in the plaque. Hepatic lipase can then catalyze the conversion of IDL to LDL by breaking down triacylglycerides in IDL and release free fatty acids to be used by other cells with low concentrations of cholesterol or stored in the liver for later use. The human body contains two inactive forms of HL. One inactive form is found on the liver bound to"
"liquid droplets. These droplets are responsible for the foamy appearance of the macrophage and thus the name of foam cells. At this point, foam cells can either be degraded though the de-esterification and secretion of cholesterol, or can further promote foam cell development and plaque formation – a process that is dependent on the balance of free cholesterol and esterified cholesterol. Low-density lipoprotein (LDL) cholesterol (LDL-C — also known as “bad” cholesterol) and particularly modified forms of LDL cholesterol such as oxidized, glycated, or acetylated LDL , is contained by a foam cell - a marker of atherosclerosis. The uptake"
"Apolipoprotein B Apolipoprotein B (ApoB) is a protein that in humans is encoded by the ""APOB"" gene. Apolipoprotein B is the primary apolipoprotein of chylomicrons, VLDL, IDL, and LDL particles (LDL - known commonly by the misnomer ""bad cholesterol"" when in reference to both heart disease and vascular disease in general), which is responsible for carrying fat molecules (lipids), including cholesterol, around the body (within the water outside cells) to all cells within all tissues. While all the functional roles of ApoB within the LDL (and all larger) particles remains somewhat unclear, it is the primary organizing protein (of the"
"LDL particle. Absorption occurs through endocytosis, and the internalized LDL particles are hydrolyzed within lysosomes, releasing lipids, chiefly cholesterol. Inflammation, a biological system response to stimuli such as the introduction of a pathogen, has an underlying role in a number of systemic biological functions and pathologies. This is a useful response by the immune system when the body is exposed to pathogens, such as bacteria in locations that will prove harmful, but can also have detrimental effects if left unregulated. It has been demonstrated that lipoproteins, specifically HDL, have important roles in the inflammatory process. When the body is functioning"
"Lipopolysaccharide Lipopolysaccharides (LPS), also known as lipoglycans and endotoxins, are large molecules consisting of a lipid and a polysaccharide composed of O-antigen, outer core and inner core joined by a covalent bond; they are found in the outer membrane of Gram-negative bacteria. The term ""lipooligosaccharide"" (""LOS"") is used to refer to a low-molecular-weight form of bacterial lipopolysaccharides. The toxic activity of LPS was first discovered and termed ""endotoxin"" by Richard Friedrich Johannes Pfeiffer, who distinguished between exotoxins, which he classified as a toxin that is released by bacteria into the surrounding environment, and endotoxins, which he considered to be a"
"the lipid hypothesis, since cholesterol (like all fat molecules) is transported around the body (in the water outside cells) inside lipoprotein particles, elevated cholesterol concentrations (hypercholesterolemia) potentially offer a lower cost way to estimate concentrations of LDL particles; possibly even low concentrations of functional HDL particles, both variations strongly associated with cardiovascular disease because LDL particles promote atheroma development in arteries (atherosclerosis). This atherosclerotic disease process, over decades, leads to myocardial infarction (heart attack), stroke, and peripheral vascular disease. Since higher blood LDL, especially higher LDL particle concentrations and smaller LDL particle size, contribute to this process more than the"
"on a community cohort study (the Malmo Diet and Cancer study) and four additional randomized controlled trials of primary prevention cohorts (JUPITER and ASCOT) and secondary prevention cohorts (CARE and PROVE IT-TIMI 22). LDL receptor The Low-Density Lipoprotein (LDL) Receptor (LDL-R) is a mosaic protein of 839 amino acids (after removal of 21-amino acid signal peptide) that mediates the endocytosis of cholesterol-rich LDL. It is a cell-surface receptor that recognizes the apoprotein B100, which is embedded in the outer phospholipid layer of LDL particles. The receptor also recognizes the apoE protein found in chylomicron remnants and VLDL remnants (IDL). In"
"or artificial origin equally raise LDL and lower HDL levels. Other studies though have shown different results when it comes to animal based trans fats like conjugated linoleic acid (CLA). Although CLA is known for its anticancer properties, researchers have also found that the cis-9, trans-11 form of CLA can reduce the risk for cardiovascular disease and help fight inflammation. Partially hydrogenated vegetable oils have been an increasingly significant part of the human diet for about 100 years (in particular, since the later half of the 20th century and where more processed foods are consumed), and some deleterious effects of"
"of the ORL1 gene in response to oxidized low-density lipoprotein cholesterol, but this has not yet been demonstrated in a living animal or human. OLR1 Oxidized low-density lipoprotein receptor 1 (Ox-LDL receptor 1) also known as lectin-type oxidized LDL receptor 1 (LOX-1) is a protein that in humans is encoded by the ""OLR1"" gene. LOX-1 is the main receptor for oxidized LDL on endothelial cells, macrophages, smooth muscle cells, and other cell types. But minimally oxidized LDL is more readily recognized by the TLR4 receptor, and highly oxidized LDL is more readily recognized by the CD36 receptor. LOX-1 is a"
"various other proteins, most notably, LDL receptor. The LDL receptor is transported to the liver cell membrane and binds to passing LDL and VLDL particles (colloquially, ""bad cholesterol""), mediating their uptake into the liver, where the cholesterol is reprocessed into bile salts and other byproducts. This results in a net effect of less LDL circulating in blood. Statins, by inhibiting the HMG CoA reductase pathway, simultaneously inhibit the production of both cholesterol and specific prenylated proteins (see diagram).This inhibitory effect on protein prenylation may be involved, at least partially, in the improvement of endothelial function, modulation of immune function, and"
"on health is still larger in older people. Elevated levels of the lipoprotein fractions, LDL, IDL and VLDL are regarded as atherogenic (prone to cause atherosclerosis). Levels of these fractions, rather than the total cholesterol level, correlate with the extent and progress of atherosclerosis. Conversely, the total cholesterol can be within normal limits, yet be made up primarily of small LDL and small HDL particles, under which conditions atheroma growth rates would still be high. Recently, a ""post hoc"" analysis of the IDEAL and the EPIC prospective studies found an association between high levels of HDL cholesterol (adjusted for apolipoprotein"
"They are classified on the basis of electrophoresis, ultracentrifugation and nuclear magnetic resonance spectroscopy via the Vantera Analyzer. For young healthy research subjects, ~70 kg (154 lb), this data represents averages across individuals studied, percentages represent % dry weight: It is also possible to classify lipoproteins as ""alpha"" and ""beta"", according to the classification of proteins in serum protein electrophoresis. This terminology is sometimes used in describing lipid disorders such as abetalipoproteinemia. Lipoproteins, such as LDL and HDL, can be further subdivided into subspecies isolated through a variety of methods . These subspecies are subdivided by density or by the"
"intermediate-density lipoprotein (IDL), which is capable of scavenging cholesterol from the blood. This converts IDL into low-density lipoprotein (LDL), which is taken up by cells that require cholesterol for incorporation into their cell membranes or for synthetic purposes (e.g. the formation of the steroid hormones). The remainder of the LDLs is removed by the liver. Adipose tissue and lactating mammary glands also take up glucose from the blood for conversion into triglycerides. This occurs in the same way as it does in the liver, except that these tissues do not release the triglycerides thus produced as VLDL into the blood."
"Chylomicron Chylomicrons (from the Greek χυλός, chylos, meaning ""juice"" (of plants or animals), and micron, meaning ""small particle"") are lipoprotein particles that consist of triglycerides (85–92%), phospholipids (6–12%), cholesterol (1–3%), and proteins (1–2%). They transport dietary lipids from the intestines to other locations in the body. Chylomicrons are one of the five major groups of lipoproteins: chylomicrons (a.k.a. ULDL ultra low-density lipoprotein relative to surrounding water), very low-density lipoprotein, intermediate-density lipoprotein, low-density lipoprotein, high-density lipoprotein, that enable fats and cholesterol to move within the water-based solution of the bloodstream. Chylomicrons transport lipids absorbed from the intestine to adipose, cardiac, and"
"widely available and increasingly regarded as important for assessing individual risk for progressive arterial disease and treatment methods. Since the HDL particles have a net negative charge and vary by density & size, ultracentrifugation combined with electrophoresis have been utilized since before 1950 to enumerate the concentration of HDL particles and sort them by size with a specific volume of blood plasma. Larger HDL particles are carrying more cholesterol. Concentration and sizes of lipoprotein particles can be estimated using nuclear magnetic resonance fingerprinting. The HDL particle concentrations are typically categorized by event rate percentiles based on the people participating and"
"forms are more easily retained by the proteoglycans. A complex set of biochemical reactions regulates the oxidation of LDL particles, chiefly stimulated by presence of necrotic cell debris and free radicals in the endothelium. Increased concentrations of LDL particles is strongly associated with the development of atherosclerosis over time. Each native LDL particle enables emulsification, i.e. surrounding/packaging all fatty acids being carried, enabling these fats to move around the body within the water outside cells. Each particle contains a single apolipoprotein B-100 molecule (Apo B-100, a protein that has 4536 amino acid residues and a mass of 514 kDa), along"
"understood. Stanol ester Stanol ester is a heterogeneous group of chemical compounds known to reduce the level of low-density lipoprotein (LDL) cholesterol in blood when ingested, though to a much lesser degree than prescription drugs such as statins. The starting material is phytosterols from plants. These are first hydrogenated to give a plant stanol which is then esterified with a mixture of fatty acids also derived from plants. Plant stanol esters are found naturally occurring in small quantities in fruits, vegetables, nuts, seeds, cereals, legumes, and vegetable oils. Stanol ester is often added to rapeseed oil based margarine or other"