High density lipoprotein

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High-density lipoprotein or high density lipoprotein is one of several lipoprotein classes in the human body, the historical reasons for their behavior in the ultracentrifuge  - and according to their density ( density are classified -). The terms HDL and alpha lipoprotein are often used synonymously in the scientific literature.

Lipoproteins are delivery vehicles made up of proteins and lipids . In the blood plasma they transport fat-like ( lipophilic ) substances such as cholesterol , cholesterol esters , triglycerides , fatty acids and phospholipids .

Function of HDL

HDL plays a central role in the metabolism of cholesterol in the human body. As a component of all cell membranes in the body, cholesterol is on the one hand indispensable for the human organism; on the other hand, too large amounts of cholesterol lead to problems, for example if the cholesterol is deposited in the blood vessels .

The main task of the HDL in this context is to transport excess cholesterol from the peripheral tissues, for example from the walls of blood vessels, back to the liver . Here the cholesterol can then be converted into bile acids and excreted in the bile. This cholesterol transport in the direction of the liver is called reverse cholesterol transport . It is essential to keep the cholesterol metabolism in balance.

Recent research shows that HDL, in addition to its function as the most important molecule for the removal of cholesterol, is also involved in the transport of other lipophilic substances. Substances that are necessary for vasodilation , for the synthesis of nitric oxide (NO), for the activation of blood platelets and blood clotting , for example , are also transported with the help of HDL particles.

Origin of HDL

Lipid-free precursor molecules such as apolipoprotein A1 (ApoA1) are formed in the liver and intestinal epithelium . The accumulation of phospholipids and non-esterified cholesterol, which are absorbed, for example, from the foam cells of the atherosclerotic plaques, gives rise to HDL precursors. Their density and volume are increased, among other things, by the activity of the enzyme lecithin cholesterol acyltransferase ( LCAT ), which esterifies non-esterified cholesterol.

The process of HDL formation is disturbed in certain hereditary diseases . In the autosomal recessive inherited Tangier disease , for example, there is a gene mutation in a protein that is responsible for removing cholesterol from the cells. As a result, HDL production is reduced and cholesterol accumulates in the tissue.

As a result, among other things, hardening and thickening of the vessel walls occur more frequently, which with a decreasing elasticity of the vessel walls and i. d. Usually also lead to narrowing of the vessel lumen.

Structure of HDL

Human HDL has a density of 1.063 to 1.210 g / ml and a size of 5 to 17 nm. It is one of the smallest and densest lipoproteins in humans. The size and density depend on the amount of lipid and protein with which HDL is loaded. HDL has a hydrophobic core in which mainly cholesterol esters and a small proportion of triglycerides and unesterified cholesterol are present. The hydrophilic shell is mainly formed from phospholipids , the apolipoproteins A1 , A2, C, E and unesterified cholesterol.

The classification of a lipoprotein as HDL is not based on its molecular structure, but on its behavior in the ultracentrifuge. It follows that the molecular composition of the HDL particles can be different. In addition to the enzyme LCAT, which is primarily involved in HDL formation, the enzyme cholesterol ester transfer protein ( CETP ) is also of outstanding importance in the context of HDL metabolism : It takes over cholesterol esters from HDL and transports them through the aqueous phase and unloads them in the case of lipoproteins of lower density ( Very Low Density Lipoproteins , Intermediate Density Lipoproteins and Low Density Lipoproteins ) in exchange for triglycerides.

Medical significance of HDL

Cholesterol is one of the central components of atherosclerotic plaques in blood vessels. Since HDL are the most important transport molecules that can transport cholesterol out of the tissue, HDL is principally anti-atherogenic. Colloquially, the cholesterol contained in HDL is therefore also called good cholesterol  - in contrast to the bad cholesterol contained in LDL , which promotes atherosclerosis . Data from numerous epidemiological and clinical studies indicate beneficial medical effects of high HDL cholesterol levels (HDL-C). For example, higher HDL-C levels in the Framingham study and in the TNT study were associated with a lower cardiovascular event rate. The influence of the HDL level was independent of the level of the LDL cholesterol level: People with a very low LDL cholesterol level and at the same time a low HDL cholesterol level had a 40 percent higher risk of cardiovascular disease than patients with a higher one HDL cholesterol levels.

Low HDL-C is therefore now regarded as a risk marker for the occurrence of cardiovascular events. Clinical studies also show that the increase in HDL cholesterol is associated with slower progression, and in some cases even with a decrease (regression) in atherosclerosis.

From a pathophysiological point of view, protection against atherosclerosis through the HDL-mediated removal of cholesterol is based on the following partial effects:

  • Promotion of the removal of cholesterol from the foam cells into the liver and thereby regression of atherosclerotic plaques
  • Improvement of the function of endothelial cells in the blood vessel wall
  • Anti-apoptotic effect
  • Anti-thrombotic effect
  • Inhibition of the expression of endothelial cell adhesion molecules and of the monocyte chemotactic protein-1 ( MCP-1 ). This prevents inflammation of the vascular wall and thus reduces the tendency to develop atherosclerotic plaques.
  • Promoting the repair of injured endothelium by promoting the proliferation of endothelial cells

Reference ranges

The individual HDL-C level can be determined as part of a lipid profile in medical laboratories. A typical lipid profile in everyday medical practice consists of total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides. The US National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) defines low HDL-C as an HDL-C value of less than 40 mg / dl and describes a low HDL-C value as an independent risk factor for a coronary artery disease. The German Lipid League agrees with this assessment in its recommendations for the diagnosis and therapy of lipid metabolism disorders in medical practice . It points out that even with normal total cholesterol (less than 200 mg / dl) there may be an increased risk of atherosclerosis if the HDL cholesterol is below 40 mg / dl. The German Society for Prevention and Rehabilitation of Cardiovascular Diseases (DGPR) has also included HDL cholesterol in its catalog of therapy goals in the context of cardiac rehabilitation after a heart attack . Raising HDL cholesterol to levels over 35 mg / dl in men and over 45 mg / dl in women is considered a goal in the treatment of disorders of lipid metabolism.

As a rule of thumb, it is now assumed that an increase in HDL-C levels by one percentage point lowers the risk of cardiovascular events by at least one percent.

Influencing factors

Low HDL-C levels can be caused by genetic factors, medical conditions, and lifestyle factors. For example, low HDL-C levels occur in type 2 diabetes , lack of exercise, smokers, people who are overweight and in patients with elevated serum triglycerides.

Conversely, lifestyle factors can increase the individual HDL-C value by around 10 to a maximum of 20 percent. These include, above all, physical activity, a low-calorie diet and giving up cigarettes . Moderate alcohol consumption also increases the HDL-C level.

Drug increase in HDL-C

Against the background of the protective effect of increased HDL-C levels with a view to cardiovascular events, drug therapies are increasingly being developed with which the HDL-C value can be increased for the purpose of preventing cardiovascular diseases or cardiovascular events. From the arsenal of classic lipid therapy, fibrates and nicotinic acid preparations in particular have a beneficial influence on HDL-C levels. However, both therapeutic approaches also influence other parameters of lipid metabolism such as LDL and triglycerides, which is why an HDL-specific effect is difficult to demonstrate.

A specific drug therapy strategy to increase HDL-C is the inhibition of the cholesterol ester transfer protein ( CETP ). The main function of CETP is the transfer of cholesterol esters from HDL to (V) LDL in exchange for triglycerides. Inhibiting CETP leads, among other things, to an increase in the HDL concentration, the apolipoprotein A1 concentration, the HDL particle size and the total HDL particle number. Via these and other mechanisms, CETP inhibition had an anti-atherogenic effect in preclinical models and initial clinical studies, which could complement the current standard therapy in secondary cardiovascular prevention. This therapeutic approach is currently being tested in large-scale studies.

literature

Web links

Wiktionary: HDL  - explanations of meanings, word origins, synonyms, translations

Individual evidence

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  2. ↑ a b Barter / Rye: A new therapeutic target: cholesteryl ester transfer protein. Current status and future directions , Birmingham: 2008
  3. ↑ Von Eckardstein et al .: Arteriosclerosis, Thrombosis, and Vascular Biology 2000; 20: 13-27
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  5. ↑ Nofer et al .: Atherosclerosis 2002; 161 (1): 1-16
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  10. ↑ Barter et al .: Eur Heart J Suppl. 2004; 6 (suppl. A): A19-A22
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  12. ↑ a b c d Calabresi et al .: Arteriosclerosis, Thrombosis, and Vascular Biology 2003; 23: 1724-1731
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  14. ↑ a b National Cholesterol Education Program (NCEP): Expert Planel on Detection, Evaluation, an Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Final Report 2002
  15. ↑ Lipid League: Recommendations for the diagnosis and therapy of lipid metabolism disorders in medical practice , May 2009
  16. ↑ German Society for Prevention and Rehabilitation of Cardiovascular Diseases: Pocket Guideline for the Rehabilitation of Patients with Cardiovascular Diseases , May 2008
  17. ^ American Diabetes Association : Diabetes Care . 2004; 27 (suppl.): 68-71
  18. ↑ Krauss et al .: Diabetes Care. 2004; 27 (suppl.): 1496-1504
  19. ↑ Belalcazar et al .: Progress Cardiovasc Dis. 1998; 41: 154-174