High density lipoprotein ( HDL ) is one of the five major groups of lipoproteins. Lipoprotein is a complex particle consisting of several proteins that transport all lipids (lipids) around the body in water outside the cells. They typically consist of 80-100 proteins per particle (composed by one, two or three ApoAs; more as the particles enlarge take and carry more fat molecules) and transport up to hundreds of fat molecules per particle.
Video High-density lipoprotein
Ikhtisar
HDL particles have long been divided into 5 subgroups, based on density/size (inverse relationship), which also correlates with the function and incidence of cardiovascular events. Unlike larger lipoprotein particles that carry fatty molecules to cells, HDL particles remove fat molecules from cells that need to export fat molecules. The lipids carried include cholesterol, phospholipids, and triglycerides, each amount varied considerably.
Increased concentrations of HDL particles are strongly associated with decreased accumulation of atherosclerosis in artery walls. This is important because atherosclerosis eventually results in sudden outbreaks of plaque, cardiovascular disease, stroke and other vascular diseases. HDL particles are sometimes referred to as "good cholesterol" because they can transport fat molecules out of the arterial wall, reducing the accumulation of macrophages, and thus help prevent or even regress atherosclerosis. However, studies have shown that mice lacking HDL still have the ability to transport cholesterol to bile, suggesting that there is an alternative mechanism to remove cholesterol.
Maps High-density lipoprotein
Test
Due to the high cost of direct measurement of HDL and LDL protein particles, blood tests are usually performed for a replacement value, HDL-C, which is cholesterol associated with ApoA-1/HDL particles. In healthy individuals, about 30% of blood cholesterol, along with other fats, is carried by HDL. This often contrasts with the amount of cholesterol that is thought to be carried in the particles of low-density lipoprotein, LDL, and is called LDL-C. HDL particles remove fat and cholesterol from the cells, including inside the atheroma artery wall, and bring it back to the liver for excretion or re-use; so the cholesterol carried in HDL particles (HDL-C) is sometimes called "good cholesterol" (although it's the same as cholesterol in LDL particles). Those with higher HDL-C levels tend to have fewer problems with cardiovascular disease, whereas those with low HDL-C cholesterol (especially less than 40 mg/dL or about 1 mmol/L) have increased rates for heart disease. Higher HDL levels correlate with better cardiovascular health; However, it does not appear that increasing one's HDL increases cardiovascular outcomes.
The rest of the serum cholesterol after HDL is reduced is non-HDL cholesterol . The concentration of these other components, which can cause atheroma, is known as non-HDL-C . It is now preferred LDL-C as a secondary marker because it has proved to be a better predictor and more easily calculated.
Structure and function
HDL is the smallest particle of lipoprotein. It is the most dense because it contains the highest protein proportions for lipids. The most abundant apolipoproteins are apo A-I and apo A-II. The rare genetic variant, ApoA-1 Milano, has been documented far more effectively in protecting and fighting arterial disease; atherosclerosis. The liver synthesizes this lipoprotein as an apolipoprotein and phospholipid complex, which resembles a cholesterol-free flat ball-chromed lipoprotein particles, whose NMR structure has recently been published; The complex is capable of taking cholesterol, done internally, from the cell by interaction with the ATP A1 bundle tape carrier (ABCA1). A plasma enzyme called lecithin-cholesterol acyltransferase (LCAT) converts free cholesterol into a cholesteryl ester (a more hydrophobic form of cholesterol), which is then sequestered to the core of lipoprotein particles, eventually leading to newly synthesized HDLs to assume a spherical shape. HDL particles get bigger as they circulate through the bloodstream and incorporate more cholesterol and phospholipid molecules from cells and other lipoproteins, for example by interactions with ABCG1 transporters and phospholipid transport proteins (PLTP).
HDL carries cholesterol mostly to liver or steroidogenic organs such as adrenals, ovaries, and testes with direct and indirect pathways. HDL is eliminated by HDL receptors such as BI-scavengers receptor (SR-BI), which mediates cholesterol absorption from HDL. In humans, perhaps the most relevant pathway is indirect, mediated by the cholesteryl ester transfer protein (CETP). This protein exchanges triglycerides from VLDL against the cholesteryl esters of HDL. As a result, VLDL is processed into LDL, which is removed from the circulation by the LDL receptor pathway. Triglycerides are unstable in HDL, but are degraded by liver lipases so that, ultimately, the small remaining HDL particles, which restart cholesterol absorption from the cells.
Cholesterol sent to the liver is excreted into bile and, therefore, the intestines either directly or indirectly after conversion into bile acids. Delivery of HDL cholesterol to the adrenals, ovaries, and testes is important for the synthesis of steroid hormones.
Some of the steps in HDL metabolism can participate in the transport of cholesterol from fatty macrophages from the atherosclerotic arteries, called foam cells, to the liver for secretion into the bile. This pathway has been called transport of reversed cholesterol and is considered a classic protective function of HDL against atherosclerosis.
However, HDL carries many species of lipids and proteins, some of which have very low concentrations but are biologically very active. For example, HDL and its proteins and lipids help inhibit oxidation, inflammation, endothelium activation, coagulation, and platelet aggregation. All of these properties can contribute to the ability of HDL to protect against atherosclerosis, and it is not known which is the most important. In addition, a small subfraction of HDL provides protection against protozoal parasites Trypanosoma brucei brucei . This HDL subfraction, termed trypanosome lytic factor (TLF), contains a special protein that, although highly active, is unique to the TLF molecule.
In the stress response, serum amyloid A, which is one of the acute phase proteins and apolipoprotein, is under stimulation of cytokines (interleukin 1, interleukin 6), and cortisol produced in the adrenal cortex and brought to the damaged tissue is incorporated into HDL particles. On the site of inflammation, it attracts and activates the leucocytes. In chronic inflammation, its precipitation in tissue manifests itself as amyloidosis.
It has been postulated that the concentration of large HDL particles more accurately reflects the protective action, as opposed to the concentration of total HDL particles. The large HDL ratio to total HDL particles varies greatly and is only measured by more sophisticated lipoprotein tests using electrophoresis (the original method developed in the 1970s) or newer NMR spectroscopy methods (See also nuclear magnetic resonance and spectroscopy), which developed in the 1990s.
Subfraction
Five HDL subfractions have been identified. Of the largest (and most effective in cholesterol removal) to the smallest (and least effective), the types are 2a, 2b, 3a, 3b, and 3c.
The ultimate lipid in the human body
Lipids are a group of heterogeneous compounds that are relatively insoluble in water and soluble in non-polar solvents. Triglycerides (TG), cholesterol, and phospholipids are the major lipids in the body. They are transported as lipid complexes and proteins known as lipoproteins.
TG (triglycerides): TG is formed by combining glycerol with three fatty acid molecules. TG, as a major component of VLDL and kilomikron, plays an important role in metabolism. When the body needs fatty acids as a source of energy, glucagon hormone marks the breakdown of TG by lipase to release free fatty acids (FFA). TG is a non-polar neutral fat that is insoluble in water. This is not a structural component of the biological membrane. The synthesis and storage of TG mostly occurs in the liver and adipose tissue. FFA and glycerol must be activated before TG synthesis becomes Acyl-CoA and glycerol-3-phosphate respectively.
Cholesterol: The cholesterol name comes from the Greek chole- (bile) and stereo (solid), and chemical-ol-ol for alcohol. It is an important structural component of cell membranes, where necessary to establish proper membrane permeability and fluidity. In addition, cholesterol is an important component for the manufacture of bile acids, steroid hormones, and vitamin D. Although cholesterol is an important and important molecule, high serum cholesterol levels are indicators for diseases such as heart disease. Approximately 20-25% of total daily cholesterol production occurs in the liver.
Phospholipids: Phospholipids are TGs that are covalently bound to the phosphate group by the ester relationship. Phospholipids perform important functions including regulating membrane permeability and maintaining the electron transport chain in the mitochondria. They participate in the transport of reverse cholesterol and thus assist in the removal of cholesterol from the body. They are involved in transmitting signals across the membranes and they act as detergents and help in the dissolution of cholesterol.
Lipoproteins: These consist of central nuclei of hydrophobic lipids (including TG and cholesteryl esters) enclosed in a hydrophilic layer of polar phospholipids, free cholesterol and apolipoproteins. There are six major classes of lipoproteins, differing in the relative proportions of the core lipids and apoprotein types.
- Chylomicrons
- VLDL-C particles
- IDL-C Particles
- LDL-C Particles
- HDL-C particles
- Lipoprotein (a) [LP (a)]
Epimodility
Men tend to have lower HDL levels, with smaller sizes and lower cholesterol content, than women. Men also have an increased incidence of atherosclerotic heart disease. Alcohol consumption tends to increase HDL levels, and moderate alcohol consumption is associated with cardiovascular mortality and all lower causes. Recent studies confirm the fact that HDL has a buffering role in balancing the effects of hypercoagulation in type 2 diabetics and lowering 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 HDL concentrations (over 60 mg/dL) have protective value against cardiovascular disease such as ischemic stroke and myocardial infarction. Low HDL concentrations (below 40 mg/dL for men, below 50 mg/dL for women) increase the risk for atherosclerotic disease.
Data from the Landmark Framingham Heart Study showed that, for certain LDL levels, the risk of heart disease increased 10-fold because HDL varied from high to low. However, on the contrary, for a fixed HDL level, the risk increases 3-fold because LDL varies from low to high.
Even people with very low LDL levels are exposed to increased risk if their HDL levels are not high enough.
Estimate HDL through related cholesterol
Clinical laboratories previously measured HDL cholesterol by separating other lipoprotein fractions using ultracentrifugation or chemical deposition with divalent ions such as Mg 2 , then combining the product from the cholesterol oxidation reaction to the indicator reaction. Reference methods still use a combination of these techniques. Most laboratories now use automated homogeneous analytic methods in which lipoproteins containing apo B are blocked using antibodies to apo B, then the colorimetric enzyme reaction measures cholesterol in unblocked HDL particles. HPLC can also be used. Subfractions (HDL-2C, HDL-3C) can be measured, but the clinical significance of these subfractions has not yet been determined. Measurement of reactive apo-A capacity can be used to measure HDL cholesterol but is considered less accurate.
Recommended range
The American Heart Association, NIH and NCEP provide a set of guidelines for fasting HDL levels and heart disease risk.
High LDL with low HDL levels is an additional risk factor for cardiovascular disease.
Measure concentration and HDL size
Because technology has reduced costs and clinical trials continue to demonstrate the importance of HDL, methods for measuring concentrations and HDL sizes directly (which indicate function) at lower costs have become more widely available and increasingly considered important for assessing individual risks for progressive arteries. disease and treatment methods.
Measurement of electrophoresis
Because HDL particles have a net negative charge and vary by density & amp; size, ultracentrifugation combined with electrophoresis has been used since before 1950 to calculate the concentration of HDL particles and sort them by size by the volume of certain blood plasma. The larger HDL particles carry more cholesterol.
NMR measurements
The concentration and size of the lipoprotein particles can be estimated using nuclear magnetic resonance fingerprints.
Maximum total and total HDL concentration
HDL particle concentrations are typically categorized by percentage of events based on participating people and tracked in a MESA trial, a medical research study sponsored by the National Heart, Lung, and Blood Institute of the United States.
The lowest incidence of atherosclerotic events over time occurs in those with the highest concentrations of total HDL particles (top quarters, & gt; 75%) and the highest concentration of large HDL particles. Some additional steps, including concentrations of LDL particles, concentrations of small LDL particles, VLDL concentrations, estimated insulin resistance and standard cholesterol lipid measurements (for comparison of plasma data with estimation methods discussed above) are routinely given in clinical trials.
Memory
Lipid serum fasting has been associated with short-term verbal memory. In a large sample of middle-aged adults, low HDL cholesterol was associated with poor memory and decreased levels during the five-year follow-up period were associated with a decrease in memory.
Increase HDL level
While higher HDL levels are correlated with cardiovascular health, no drug used to raise HDL has been shown to improve health. In other words, while high levels of HDL may be correlated with better cardiovascular health, especially increasing HDLs may not improve cardiovascular health. The only possibility left is that good good cardiovascular health leads to high HDL levels, there are some third factors that cause both, or this is a coincidence without causal relationship.
HDL lipoprotein particles containing apolipoprotein C3 are associated with an increase, not a decrease, the risk of coronary heart disease.
Diet and sports
Certain changes in diet and exercise can positively impact HDL levels:
- Decrease in the intake of simple carbohydrates.
- Aerobic exercise
- Weight
- Magnesium supplements increase HDL-C.
- The addition of soluble fiber to the diet
- Consumption of omega-3 fatty acids such as fish oil or flax oil
- Consumption of pistachio nuts.
- Increased intake of cis unsaturated fat
- The consumption of medium chain triglycerides (MCTs) such as caproic acid, caprylic acid, capric acid, and lauric acid.
- Eliminate trans fatty acids from diet
Most saturated fats increase HDL cholesterol to varying degrees but also increase total cholesterol and LDL. A high-protein, low-carb diogenetic ketogenic diet may have the same response to taking niacin (vitamin B5) as described below (lowering LDL and increasing HDL) through beta-hydroxybutyrate coupling of Niacin 1 receptors.
recreational drugs
HDL levels can be increased by smoking cessation, or mild to moderate alcohol intake.
Cannabis in an unadjusted analysis, past and current cannabis use is not associated with higher HDL-C levels. A study of 4635 patients showed no effect on HDL-C levels (P = 0.78) [HDL-C standard error rate in control subjects (never used), previous users and current users were 53.4 (0.4), 53.9 (0.6) and 53.9 (0.7) mg/dL, respectively].
Pharmaceutical drugs and niacin
Pharmacologic therapy to increase HDL cholesterol levels includes the use of fibrates and niacin. Fibrat has not been shown to have an effect on overall mortality from all causes, despite its effect on lipids.
Niacin (vitamin B3) increases HDL by selectively inhibiting diacylglycerol acyltransferase 2, reducing triglyceride synthesis and VLDL secretion through HM74 receptors or known as niacin 2 and HM74A/GPR109A receptors, niacin 1 receptors.
Pharmacologic (1- to 3-gram/day) dose of niacin raises HDL levels by 10-30%, making it the most powerful agent for increasing HDL-cholesterol. A randomized clinical trial showed that treatment with niacin could significantly reduce the development of atherosclerosis and cardiovascular events. However, niacin products sold as "no-flush", ie have no side effects such as "niacin flush", do not contain free nicotinic acid and are therefore ineffective in increasing HDL, while products are sold as " sustained release "may contain free nicotinic acid, but" some brands are hepatotoxic "; therefore the recommended form of niacin to raise HDL is the cheapest, immediate release preparation. Both fibrates and niacin increase artificial toxic homocysteine, a neutral effect by taking multivitamins with a relatively high amount of B vitamins, but some European experiments from the most popular B-vitamin cocktail, experiments show a 30% decrease in average in homocysteine, while do not show any problems nor show any benefit in reducing the incidence of cardiovascular events. The 2011 study of niacin was discontinued earlier because patients who added niacin to their statin treatment did not show an increase in heart health, but had an increased risk of stroke.
Conversely, while the use of statins is effective against high LDL cholesterol levels, most have little or no effect in increasing HDL cholesterol. However, some statins - rosuvastatin and pitavastatin - have been shown to significantly increase HDL levels. Because statins are associated with side effects such as myopathy that cause muscle pain, patients with these side effects may need to be given a lower statin dose to control cholesterol.
Lovaza has been shown to increase HDL-C. However, the best evidence to date has shown no benefit for the prevention of primary or secondary cardiovascular disease.
Although not yet FDA approved, the PPAR modulator (sometimes referred to as SARM) GW501516, current research chemicals (not for human consumption), has shown a positive effect on HDL-C and antiatherogenic in which LDL is an issue.
See also
- Asymmetric dimethylarginine
- Cardiovascular disease
- Cholesteryl ester storage disease
- Endothelium
- Lipid profile
- Low density lipoproteins
- Lack of liposic acid lipase deficiency
Notes and references
External links
- Adult Care Panel III Full Report - National Heart, Lung and Blood Institute
- ATP Update III 2004 - National Heart, Lung, and Blood Institute
- HDL: Good, but complex, Cholesterol, - Harvard Heart Letter
- HDL Cholesterol in the Online Test Lab
Source of the article : Wikipedia
0 Comments