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Lipoprotein

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A lipoprotein is a biochemical assembly whose primary function is to transport hydrophobic lipid (also known as fat ) molecules in water, as in blood plasma or other extracellular fluids . They consist of a triglyceride and cholesterol center, surrounded by a phospholipid outer shell, with the hydrophilic portions oriented outward toward the surrounding water and lipophilic portions oriented inward toward the lipid center. A special kind of protein, called apolipoprotein , is embedded in the outer shell, both stabilising the complex and giving it a functional identity that determines its role.

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71-593: Plasma lipoprotein particles are commonly divided into five main classes, based on size, lipid composition, and apolipoprotein content: HDL , LDL , IDL , VLDL and chylomicrons . Subgroups of these plasma particles are primary drivers or modulators of atherosclerosis . Many enzymes , transporters , structural proteins, antigens , adhesins , and toxins are sometimes also classified as lipoproteins, since they are formed by lipids and proteins. Some transmembrane proteolipids , especially those found in bacteria , are referred to as lipoproteins; they are not related to

142-416: A condition called steatorrhea . Feces lack their characteristic brown color and instead are white or gray, and greasy. Steatorrhea can lead to deficiencies in essential fatty acids and fat-soluble vitamins . In addition, past the small intestine (which is normally responsible for absorbing fat from food) the gastrointestinal tract and gut flora are not adapted to processing fats, leading to problems in

213-438: A condition when bile ducts which deliver bile from the gallbladder or liver to the duodenum become obstructed. The blockage of bile might cause a buildup of bilirubin in the bloodstream which can result in jaundice . There are several potential causes for biliary obstruction including gallstones, cancer, trauma, choledochal cysts , or other benign causes of bile duct narrowing. The most common cause of bile duct obstruction

284-522: A decrease in HDL cholesterol (HDL-C), phospholipids, apoA-I (a major lipoprotein in HDL 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

355-559: A few hours before washing as a traditional and effective method for removing various kinds of tough stains. Pinapaitan is a dish in Philippine cuisine that uses bile as flavoring. Other areas where bile is commonly used as a cooking ingredient include Laos and northern parts of Thailand . During the Boshin War , Satsuma soldiers of the early Imperial Japanese Army reportedly ate human livers boiled in bile. The practice of eating

426-914: A form of vitamin B3 ) increases HDL by selectively inhibiting hepatic diacylglycerol acyltransferase 2, reducing triglyceride synthesis and VLDL secretion through a receptor HM74 otherwise known as niacin receptor 2 and HM74A / GPR109A, niacin receptor 1 . Pharmacologic (1- to 3-gram/day) niacin doses increase HDL levels by 10–30%, making it the most powerful agent to increase HDL-cholesterol. A randomized clinical trial demonstrated that treatment with niacin can significantly reduce atherosclerosis progression and cardiovascular events. Niacin products sold as "no-flush", i.e. not having side-effects such as "niacin flush ", do not, however, contain free nicotinic acid and are therefore ineffective at raising HDL, while products sold as "sustained-release" may contain free nicotinic acid, but "some brands are hepatotoxic"; therefore

497-723: A greater incidence of atherosclerotic heart disease. Studies confirm the fact that HDL has a buffering role in balancing the effects of the hypercoagulable state in type 2 diabetics and decreases the high risk of cardiovascular complications in these patients. Also, the results obtained in this study revealed that there was a significant negative correlation between HDL and activated partial thromboplastin time (APTT). Epidemiological studies have shown that high concentrations of HDL (over 60 mg/dL) have protective value against cardiovascular diseases such as ischemic stroke and myocardial infarction . Low concentrations of HDL (below 40 mg/dL for men, below 50 mg/dL for women) increase

568-427: A hydrophilic external shell that functions as a transport vehicle. The role of lipoprotein particles is to transport fat molecules, such as triglycerides , phospholipids, and cholesterol within the extracellular water of the body to all the cells and tissues of the body. The proteins included in the external shell of these particles, called apolipoproteins, are synthesized and secreted into the extracellular water by both

639-520: A layer of unclotted erythrocytes ("blood"), a layer of white blood cells ("phlegm") and a layer of clear yellow serum ("yellow bile"). Excesses of black bile and yellow bile were thought to produce depression and aggression, respectively, and the Greek names for them gave rise to the English words cholera (from Greek χολή kholē , "bile") and melancholia . In the former of those senses, the same theories explain

710-417: A person's vomit may be green or dark yellow, and very bitter. The bitter and greenish component may be bile or normal digestive juices originating in the stomach. Bile may be forced into the stomach secondary to a weakened valve ( pylorus ), the presence of certain drugs including alcohol , or powerful muscular contractions and duodenal spasms. This is known as biliary reflux . Biliary obstruction refers to

781-426: A positive impact on raising HDL levels: Most saturated fats increase HDL cholesterol to varying degrees but also raise total and LDL cholesterol. HDL levels can be increased by smoking cessation , or mild to moderate alcohol intake. Cannabis in unadjusted analyses, past and current cannabis use was not associated with higher HDL-C levels. A study performed in 4635 patients demonstrated no effect on

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852-640: A relatively high cholesterol content ( see native LDL structure at 37°C on YouTube ). LDL circulates and is absorbed by the liver and peripheral cells. Binding of LDL to its target tissue occurs through an interaction between the LDL receptor and apolipoprotein B-100 on the LDL particle. Absorption occurs through endocytosis , and the internalized LDL particles are hydrolyzed within lysosomes, releasing lipids, chiefly cholesterol. Plasma lipoproteins may carry oxygen gas. This property

923-495: A significant risk factor for atherosclerotic cardiovascular diseases via mechanisms associated with inflammation and thrombosis . The links of mechanisms between different lipoprotein isoforms and risk for cardiovascular diseases, lipoprotein synthesis, regulation, and metabolism, and related risks for genetic diseases are under active research, as of 2022. High-density lipoprotein High-density lipoprotein ( HDL )

994-411: Is a yellow-green fluid or it could be a green misty colour produced by the liver of most vertebrates that aids the digestion of lipids in the small intestine . In humans, bile is primarily composed of water , produced continuously by the liver, and stored and concentrated in the gallbladder . After a human eats, this stored bile is discharged into the first section of the small intestine . In

1065-412: 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. HDL has the ability to bind LPS and LTA, creating HDL-LPS complexes to neutralize the harmful effects in

1136-424: Is associated with increased mortality and worse clinical outcomes in patients with sepsis. Lipoproteins may be classified as five major groups, listed from larger and lower density to smaller and higher density. Lipoproteins are larger and less dense when the fat to protein ratio is increased. They are classified on the basis of electrophoresis , ultracentrifugation and nuclear magnetic resonance spectroscopy via

1207-473: Is divided into two pathways, exogenous and endogenous , depending in large part on whether the lipoprotein particles in question are composed chiefly of dietary (exogenous) lipids or whether they originated in the liver (endogenous), through de novo synthesis of triglycerides. The hepatocytes are the main platform for the handling of triglycerides and cholesterol; the liver can also store certain amounts of glycogen and triglycerides. While adipocytes are

1278-612: Is due to the crystalline hydrophobic structure of lipids, providing a suitable environment for O 2 solubility compared to an aqueous medium. Inflammation , a biological system response to stimuli such as the introduction of a pathogen , has an underlying role in numerous 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

1349-661: Is important for the synthesis of steroid hormones . Several steps in the metabolism of HDL can participate in the transport of cholesterol from lipid-laden macrophages of atherosclerotic arteries , termed foam cells , to the liver for secretion into the bile. This pathway has been termed reverse cholesterol transport and is considered as the classical protective function of HDL toward atherosclerosis. HDL carries many lipid and protein species, several of which have very low concentrations but are biologically very active. For example, HDL and its protein and lipid constituents help to inhibit oxidation , inflammation , activation of

1420-635: 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. Lipoproteins are divided into five subgroups, by density/size (an inverse relationship), which also correlates with function and incidence of cardiovascular events. Unlike

1491-589: Is produced per day in adult human beings. Bile or gall acts to some extent as a surfactant , helping to emulsify the lipids in food. Bile salt anions are hydrophilic on one side and hydrophobic on the other side; consequently, they tend to aggregate around droplets of lipids ( triglycerides and phospholipids ) to form micelles , with the hydrophobic sides towards the fat and hydrophilic sides facing outwards. The hydrophilic sides are negatively charged, and this charge prevents fat droplets coated with bile from re-aggregating into larger fat particles. Ordinarily,

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1562-412: Is removed by HDL receptors such as scavenger receptor BI (SR-BI), which mediate the selective uptake of cholesterol from HDL. In humans, probably the most relevant pathway is the indirect one, which is mediated by cholesteryl ester transfer protein (CETP) . This protein exchanges triglycerides of VLDL against cholesteryl esters of HDL. As the result, VLDLs are processed to LDL , which are removed from

1633-430: Is some evidence that the HDL reduction is caused by increased reverse cholesterol transport , it is unknown if AR agonists' HDL-lowering effect is pro- or anti-atherogenic. Pharmacological therapy to increase the level of HDL cholesterol includes use of fibrates and niacin . Fibrates have not been proven to have an effect on overall deaths from all causes, despite their effects on lipids. Niacin (nicotinic acid,

1704-512: 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 are subdivided by density or by the protein contents/ proteins they carry. While the research is currently ongoing, researchers are learning that different subspecies contain different apolipoproteins, proteins, and lipid contents between species which have different physiological roles. For example, within

1775-416: Is surrounded by a hydrophilic membrane consisting of phospholipids, free cholesterol, and apolipoproteins. Plasma lipoproteins, found in blood plasma , are typically divided into five main classes based on size, lipid composition, and apolipoprotein content: HDL , LDL , IDL , VLDL and chylomicrons . The handling of lipoprotein particles in the body is referred to as lipoprotein particle metabolism . It

1846-504: Is the densest because it contains the highest proportion of protein to lipids . Its most abundant apolipoproteins are apo A-I and apo A-II . A rare genetic variant, ApoA-1 Milano , has been documented to be far more effective in both protecting against and regressing arterial disease, atherosclerosis . The liver synthesizes these lipoproteins as complexes of apolipoproteins and phospholipid, which resemble cholesterol-free flattened spherical lipoprotein particles, whose NMR structure

1917-580: Is then considered mature. Via apolipoprotein C-II, mature chylomicrons activate lipoprotein lipase (LPL), an enzyme on endothelial cells lining the blood vessels. LPL catalyzes the hydrolysis of triglycerides that ultimately releases glycerol and fatty acids from the chylomicrons. Glycerol and fatty acids can then be absorbed in peripheral tissues, especially adipose and muscle , for energy and storage. The hydrolyzed chylomicrons are now called chylomicron remnants . The chylomicron remnants continue circulating

1988-636: Is thought to be less accurate. The American Heart Association , NIH and NCEP provide a set of guidelines for fasting HDL levels and risk for heart disease . High LDL with low HDL level is an additional risk factor for cardiovascular disease. As technology has reduced costs and clinical trials have continued to demonstrate the importance of HDL, methods for directly measuring HDL concentrations and size (which indicates function) at lower costs have become more widely available and increasingly regarded as important for assessing individual risk for progressive arterial disease and treatment methods. Since

2059-457: Is when gallstone(s) are dislodged from the gallbladder into the cystic duct or common bile duct resulting in a blockage. A blockage of the gallbladder or cystic duct may cause cholecystitis . If the blockage is beyond the confluence of the pancreatic duct, this may cause gallstone pancreatitis . In some instances of biliary obstruction, the bile may become infected by bacteria resulting in ascending cholangitis . In medical theories prevalent in

2130-528: The Vantera Analyzer . For young healthy research subjects, ~70 kg (154 lb), these data represent averages across individuals studied, percentages represent % dry weight: However, these data are not necessarily reliable for any one individual or for the general clinical population. It is also possible to classify lipoproteins as "alpha" and "beta", according to the classification of proteins in serum protein electrophoresis . This terminology

2201-498: The lacteals in a process that depends heavily on apolipoprotein B-48. As they circulate through the lymphatic vessels , nascent chylomicrons bypass the liver circulation and are drained via the thoracic duct into the bloodstream. In the blood stream, nascent chylomicron particles interact with HDL particles, resulting in HDL donation of apolipoprotein C-II and apolipoprotein E to the nascent chylomicron. The chylomicron at this stage

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2272-417: The small intestine and liver cells. The external shell also contains phospholipids and cholesterol. All cells use and rely on fats and cholesterol as building blocks to create the multiple membranes that cells use both to control internal water content and internal water-soluble elements and to organize their internal structure and protein enzymatic systems. The outer shell of lipoprotein particles have

2343-400: The villi on the intestine walls. After being transferred across the intestinal membrane, the fatty acids reform into triglycerides ( re-esterified ), before being absorbed into the lymphatic system through lacteals . Without bile salts, most of the lipids in food would be excreted in feces, undigested. Since bile increases the absorption of fats, it is an important part of the absorption of

2414-442: The 1970s) or newer NMR spectroscopy methods (See also nuclear magnetic resonance and spectroscopy ), developed in the 1990s. Five subfractions of HDL have been identified. From largest (and most effective in cholesterol removal) to smallest (and least effective), the types are 2a, 2b, 3a, 3b, and 3c. Men tend to have noticeably lower HDL concentrations, with smaller size and lower cholesterol content, than women. Men also have

2485-599: The HDL lipoprotein subspecies, a large number of proteins are involved in general lipid metabolism. However, it is being elucidated that HDL subspecies also contain proteins involved in the following functions: homeostasis , fibrinogen , clotting cascade , inflammatory and immune responses, including the complement system , proteolysis inhibitors, acute-phase response proteins, and the LPS-binding protein , heme and iron metabolism, platelet regulation, vitamin binding and general transport. High levels of lipoprotein(a) are

2556-542: 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

2627-519: The HDL-C levels (P=0.78) [the mean (standard error) HDL-C values in control subjects (never used), past users and current users were 53.4 (0.4), 53.9 (0.6) and 53.9 (0.7) mg/dL, respectively]. Exogenous anabolic androgenic steroids , particularly 17α-alkylated anabolic steroids and others administered orally, can reduce HDL-C by 50 percent or more. Other androgen receptor agonists such as selective androgen receptor modulators can also lower HDL. As there

2698-476: The TLF molecule. In the stress response , serum amyloid A , which is one of the acute-phase proteins and an apolipoprotein, is under the stimulation of cytokines ( interleukin 1 , interleukin 6 ), and cortisol produced in the adrenal cortex and carried to the damaged tissue incorporated into HDL particles. At the inflammation site, it attracts and activates leukocytes. In chronic inflammations, its deposition in

2769-654: The VLDL particle and the release of glycerol and fatty acids. These products can be absorbed from the blood by peripheral tissues, principally adipose and muscle. The hydrolyzed VLDL particles are now called VLDL remnants or intermediate-density lipoproteins (IDLs). VLDL remnants can circulate and, via an interaction between apolipoprotein E and the remnant receptor, be absorbed by the liver, or they can be further hydrolyzed by hepatic lipase . Hydrolysis by hepatic lipase releases glycerol and fatty acids, leaving behind IDL remnants , called low-density lipoproteins (LDL), which contain

2840-500: The West from classical antiquity to the Middle Ages , the body's health depended on the equilibrium of four "humors" , or vital fluids, two of which related to bile: blood, phlegm , "yellow bile" (choler), and "black bile". These "humors" are believed to have their roots in the appearance of a blood sedimentation test made in open air, which exhibits a dark clot at the bottom ("black bile"),

2911-429: The best evidence to date suggests it has no benefit for primary or secondary prevention of cardiovascular disease. The PPAR modulator GW501516 has shown a positive effect on HDL-C and an antiatherogenic where LDL is an issue. However, research on the drug has been discontinued after it was discovered to cause rapid cancer development in several organs in rats. Bile Bile (from Latin bilis ), or gall ,

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2982-400: The blood, with each other, or with specific proteins on the surfaces of cells, determines whether triglycerides and cholesterol will be added to or removed from the lipoprotein transport particles. Characterization in human plasma Lipoproteins are complex particles that have a central hydrophobic core of non-polar lipids, primarily cholesteryl esters and triglycerides. This hydrophobic core

3053-411: The bloodstream until they interact via apolipoprotein E with chylomicron remnant receptors, found chiefly in the liver. This interaction causes the endocytosis of the chylomicron remnants, which are subsequently hydrolyzed within lysosomes . Lysosomal hydrolysis releases glycerol and fatty acids into the cell, which can be used for energy or stored for later use. The liver is the central platform for

3124-476: The bloodstream via a process that depends upon apolipoprotein B-100. In the blood stream, nascent VLDL particles bump with HDL particles; as a result, HDL particles donate apolipoprotein C-II and apolipoprotein E to the nascent VLDL particle. Once loaded with apolipoproteins C-II and E, the nascent VLDL particle is considered mature. VLDL particles circulate and encounter LPL expressed on endothelial cells . Apolipoprotein C-II activates LPL, causing hydrolysis of

3195-501: 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. 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

3266-445: The circulation by the LDL receptor pathway. The triglycerides are not stable in HDL, but are degraded by hepatic lipase so that, finally, small HDL particles are left, which restart the uptake of cholesterol from cells. The cholesterol delivered to the liver is excreted into the bile and, hence, intestine either directly or indirectly after conversion into bile acids . Delivery of HDL cholesterol to adrenals, ovaries, and testes

3337-496: The derivation of the English word bilious from bile , the meaning of gall in English as "exasperation" or "impudence", and the Latin word cholera , derived from the Greek kholé , which was passed along into some Romance languages as words connoting anger, such as colère (French) and cólera (Spanish). Soap can be mixed with bile from mammals, such as ox gall . This mixture, called bile soap or gall soap, can be applied to textiles

3408-454: The endothelium , coagulation , and platelet aggregation . All these properties may contribute to the ability of HDL to protect from atherosclerosis, and it is not yet known which are the most important. In addition, a small subfraction of HDL lends protection against the protozoan parasite Trypanosoma brucei brucei . This HDL subfraction, termed trypanosome lytic factor (TLF), contains specialized proteins that, while very active, are unique to

3479-450: The fat-soluble substances, such as the vitamins A , D , E , and K . Besides its digestive function, bile serves also as the route of excretion for bilirubin, a byproduct of red blood cells recycled by the liver. Bilirubin derives from hemoglobin by glucuronidation . Bile tends to be alkaline on average. The pH of common duct bile (7.50 to 8.05) is higher than that of the corresponding gallbladder bile (6.80 to 7.65). Bile in

3550-464: The gallbladder becomes more acidic the longer a person goes without eating, though resting slows this fall in pH. As an alkali, it also has the function of neutralizing excess stomach acid before it enters the duodenum, the first section of the small intestine . Bile salts also act as bactericides , destroying many of the microbes that may be present in the food. In the absence of bile, fats become indigestible and are instead excreted in feces ,

3621-492: The handling of lipids: it is able to store glycerols and fats in its cells, the hepatocytes . Hepatocytes are also able to create triglycerides via de novo synthesis. They also produce the bile from cholesterol. The intestines are responsible for absorbing cholesterol. They transfer it over into the blood stream. In the hepatocytes, triglycerides and cholesteryl esters are assembled with apolipoprotein B-100 to form nascent VLDL particles . Nascent VLDL particles are released into

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3692-592: The high cost of directly measuring HDL and LDL ( low-density lipoprotein ) protein particles, blood tests are commonly performed for the surrogate value, HDL-C, i.e. the cholesterol associated with ApoA-1 /HDL particles. In healthy individuals, about 30% of blood cholesterol, along with other fats, is carried by HDL. This is often contrasted with the amount of cholesterol estimated to be carried within low-density lipoprotein particles, LDL , and called LDL-C. HDL particles remove fats and cholesterol from cells, including within artery wall atheroma , and transport it back to

3763-438: The human liver , bile is composed of 97–98% water , 0.7% bile salts , 0.2% bilirubin , 0.51% fats ( cholesterol , fatty acids , and lecithin ), and 200 meq/L inorganic salts. The two main pigments of bile are bilirubin , which is orange-yellow, and its oxidised form biliverdin , which is green. When mixed, they are responsible for the brown color of feces . About 400 to 800 milliliters (14 to 27 U.S. fluid ounces) of bile

3834-454: The hydrophilic groups of phospholipids, cholesterol, and apolipoproteins directed outward. Such characteristics make them soluble in the salt-water-based blood pool. Triglycerides and cholesteryl esters are carried internally, shielded from the water by the outer shell. The kind of apolipoproteins contained in the outer shell determines the functional identity of the lipoprotein particles. The interaction of these apolipoproteins with enzymes in

3905-467: The inflammatory process. When the body is functioning under normal, stable physiological conditions, HDL has been shown to be beneficial in several ways. LDL contains apolipoprotein B (apoB), which allows LDL to bind to different tissues, such as the artery wall if the glycocalyx has been damaged by high blood sugar levels . If oxidised, the LDL can become trapped in the proteoglycans, preventing its removal by HDL cholesterol efflux. Normal functioning HDL

3976-471: The large intestine. The cholesterol contained in bile will occasionally accrete into lumps in the gallbladder, forming gallstones . Cholesterol gallstones are generally treated through surgical removal of the gallbladder. However, they can sometimes be dissolved by increasing the concentration of certain naturally occurring bile acids, such as chenodeoxycholic acid and ursodeoxycholic acid . On an empty stomach – after repeated vomiting , for example –

4047-917: 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 within the walls of arteries, reducing the risk of sudden plaque ruptures , cardiovascular disease , stroke and other vascular diseases . HDL particles are commonly referred to as "good cholesterol", because they transport fat molecules out of artery walls, reduce macrophage accumulation, and thus help prevent or even regress atherosclerosis. Higher HDL-C may not necessarily be protective against cardiovascular disease and may even be harmful in extremely high quantities, with an increased cardiovascular risk, especially in hypertensive patients. Because of

4118-510: The lipoprotein particles that this article is about. Such transmembrane proteins are difficult to isolate, as they bind tightly to the lipid membrane, often require lipids to display the proper structure, and can be water-insoluble. Detergents are usually required to isolate transmembrane lipoproteins from their associated biological membranes. Because fats are insoluble in water, they cannot be transported on their own in extracellular water, including blood plasma. Instead, they are surrounded by

4189-563: The liver for excretion or re-utilization; thus the cholesterol carried within HDL particles (HDL-C) is sometimes called "good cholesterol" (despite being the same as cholesterol in LDL particles). Those with higher levels of HDL-C tend to have fewer problems with cardiovascular diseases , while those with low HDL-C cholesterol levels (especially less than 40 mg/dL or about 1 mmol/L) have increased rates for heart disease. Higher native HDL levels are correlated with lowered risk of cardiovascular disease in healthy people. The remainder of

4260-536: The main storage cells for triglycerides, they do not produce any lipoproteins. Bile emulsifies fats contained in the chyme , then pancreatic lipase cleaves triglyceride molecules into two fatty acids and one 2-monoacylglycerol. Enterocytes readily absorb the small molecules from the chymus. Inside of the enterocytes, fatty acids and monoacylglycerides are transformed again into triglycerides. Then these lipids are assembled with apolipoprotein B-48 into nascent chylomicrons . These particles are then secreted into

4331-418: The micelles in the duodenum have a diameter around 1–50  μm in humans. The dispersion of food fat into micelles provides a greatly increased surface area for the action of the enzyme pancreatic lipase , which digests the triglycerides, and is able to reach the fatty core through gaps between the bile salts. A triglyceride is broken down into two fatty acids and a monoglyceride , which are absorbed by

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4402-526: The newly synthesized HDL to assume a spherical shape. HDL particles increase in size as they circulate through the blood and incorporate more cholesterol and phospholipid molecules from cells and other lipoproteins, such as by interaction with the ABCG1 transporter and the phospholipid transport protein (PLTP) . HDL transports cholesterol mostly to the liver or steroidogenic organs such as adrenals , ovary , and testes by both direct and indirect pathways. HDL

4473-724: The people participating and being tracked in the MESA trial, a medical research study sponsored by the United States National Heart, Lung, and Blood Institute. The lowest incidence of atherosclerotic events over time occurs within those with both the highest concentrations of total HDL particles (the top quarter, >75%) and the highest concentrations of large HDL particles. Multiple additional measures, including LDL particle concentrations, small LDL particle concentrations, VLDL concentrations, estimations of insulin resistance and standard cholesterol lipid measurements (for comparison of

4544-593: The plasma data with the estimation methods discussed above) are routinely provided in clinical testing. While higher HDL levels are correlated with lower risk of cardiovascular diseases, no medication used to increase HDL has been proven to improve health. As of 2017, numerous lifestyle changes and drugs to increase HDL levels were under study. HDL lipoprotein particles that bear apolipoprotein C3 are associated with increased, rather than decreased, risk for coronary heart disease . Certain changes in diet and exercise may have

4615-616: The products of a cholesterol oxidase reaction to an indicator reaction. The reference method still uses a combination of these techniques. Most laboratories now use automated homogeneous analytical methods in which lipoproteins containing apo B are blocked using antibodies to apo B, then a colorimetric enzyme reaction measures cholesterol in the non-blocked HDL particles. HPLC can also be used. Subfractions (HDL-2C, HDL-3C) can be measured, but clinical significance of these subfractions has not been determined. The measurement of apo-A reactive capacity can be used to measure HDL cholesterol but

4686-597: The recommended form of niacin for raising HDL is the cheapest, immediate-release preparation. Both fibrates and niacin increase artery toxic homocysteine , an effect that can be counteracted by also consuming a multivitamin with relatively high amounts of the B-vitamins, but multiple European trials of the most popular B-vitamin cocktails, trial showing 30% average reduction in homocysteine, while not showing problems have also not shown any benefit in reducing cardiovascular event rates. A 2011 extended-release niacin (Niaspan) study

4757-672: The risk for atherosclerotic diseases. Data from the landmark Framingham Heart Study showed that, for a given level of LDL, the risk of heart disease increases 10-fold as the HDL varies from high to low. On the converse, however, for a fixed level of HDL, the risk increases 3-fold as LDL varies from low to high. Even people with very low LDL levels achieved by statin treatment are exposed to increased risk if their HDL levels are not high enough. Clinical laboratories formerly measured HDL cholesterol by separating other lipoprotein fractions using either ultracentrifugation or chemical precipitation with divalent ions such as Mg , then coupling

4828-413: The serum cholesterol after subtracting the HDL is the non-HDL cholesterol . The concentration of these other components, which may cause atheroma , is known as the non-HDL-C . This is now preferred to LDL-C as a secondary marker as it has been shown to be a better predictor and it is more easily calculated. With a size ranging from 5 to 17 nm, HDL is the smallest of the lipoprotein particles. It

4899-406: The tissues manifests itself as amyloidosis . It has been postulated that the concentration of large HDL particles more accurately reflects protective action, as opposed to the concentration of total HDL particles. This ratio of large HDL to total HDL particles varies widely and is measured only by more sophisticated lipoprotein assays using either electrophoresis (the original method developed in

4970-476: Was halted early because patients adding niacin to their statin treatment showed no increase in heart health, but did experience an increase in the risk of stroke. In contrast, while the use of statins is effective against high levels of LDL cholesterol, most have little or no effect in raising HDL cholesterol. Rosuvastatin and pitavastatin , however, have been demonstrated to significantly raise HDL levels. Lovaza has been shown to increase HDL-C. However,

5041-478: Was published; the complexes are capable of picking up cholesterol, carried internally, from cells by interaction with the ATP-binding cassette transporter A1 (ABCA1) . A plasma enzyme called lecithin-cholesterol acyltransferase (LCAT) converts the free cholesterol into cholesteryl ester (a more hydrophobic form of cholesterol), which is then sequestered into the core of the lipoprotein particle, eventually causing

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