High-density lipoprotein reverse cholesterol

High-Density Lipoprotein Reverse Cholesterol Transfer Pathway... 

Niacin effectively raises high density lipoprotein (HDL) cholesterol levels. In the absence of HDL, peripheral tissues accumulate cholesterol, presumably due to lack of reverse cholesterol transport from peripheral tissues to the liver. Niacin inhibits the degradation of HDL protein by HepG2 cells, potentially by downregulating cell surface expression of the ATP synthase beta chain. 

Figure 25-5. Metabolism of high-density lipoprotein (HDL) in reverse cholesteroi transport. (LCAT, lecithinxholesterol acyltransferase C, cholesterol CE, cholesteryl ester PL, phospholipid A-l, apolipoprotein A-l SR-Bl, scavenger receptor B1 ABC-1, ATP binding cassette transporter 1.) Prep-HDL, HDLj, HDL3—see Table 25-1. Surplus surface constituents from the action of lipoprotein lipase on chylomicrons and VLDL are another source of preP-HDL. Hepatic lipase activity is increased by androgens and decreased by estrogens, which may account for higher concentrations of plasma HDLj in women.

Four major groups of lipoproteins are recognized Chylomicrons transport lipids resulting from digestion and absorption. Very low density lipoproteins (VLDL) transport triacylglycerol from the liver. Low-density lipoproteins (LDL) deliver cholesterol to the tissues, and high-density lipoproteins (HDL) remove cholesterol from the tissues in the process known as reverse cholesterol transport. 

One role of high density lipoprotein (HDL) is to collect unesterified cholesterol from cells, including endothelial cells of the artery walls, and return it to the liver where it can not only inhibit cholesterol synthesis but also provide the precursor for bile acid formation. The process is known as reverse cholesterol transfer and its overall effect is to lower the amount of cholesterol in cells and in the blood. Even an excessive intracellular level of cholesterol can be lowered by this reverse transfer process (Figure 22.10). Unfortunately, the level of HDL in the subendothelial space of the arteries is very low, so that this safety valve is not available and all the cholesterol in this space is taken up by the macrophage to form cholesteryl ester. This is then locked within the macrophage (i.e. not available to HDL) and causes damage and then death of the cells, as described above. 

Figure 22.10 Reverse cholesterol transfer. High density lipoprotein (HDL) collects cholesterol from cells in various tissues/ organs the complex is then transported in the blood to the liver where it binds to a receptor on the hepatocyte, is internalised and the cholesterolis released into the hepatocyte. This increases the concentration in the liver cells which then decreases the synthesis of cholesterol by inhibition of the rate-limiting enzyme in cholesterol synthesis, HMG-CoA synthase. The cholesterol is also secreted into the bile or converted to bile acids which are also secreted into the bile, some of which is lost in the faeces (Chapter A).

Whole plasma can also be fractionated into specific lipoprotein size classes to further resolve the underlying biochemistry and metabolism of tissues that deliver these lipids to blood and selectively remove them. Thus, TrueMass analysis can be used to measure the lipid profiles of very-low-density lipoprotein, quantify the lipid pathways responsible for metabolic changes in the liver and measure profiles of high-density lipoprotein to quantify the flux of lipids in reverse cholesterol transport. 

Babiker A, Andersson O, Lund E, et al. Elimination of cholesterol in macrophages and endothelial cells by the sterol 27-hydroxylase mechanism. Comparison with high-density lipoprotein-mediated reverse cholesterol transport. J Biol Chem 1997 272 26253-26261. 

Profiling of plasma lipoproteins and serum lipids can often aid in the diagnosis of Tangier disease. There are four classes of lipoproteins (1) chylomicrons, which transport dietary cholesterol and triglycerides from the intestines to the tissues (2) very low-density lipoproteins (VLDL) and (3) low-density lipoproteins (LDL), both of which transport de novo synthesized cholesterol and triglyceride from the liver to the tissues and (4) high-density lipoproteins (HDL), which mediate reverse cholesterol transport, a process in which excess cholesterol from peripheral tissues is transported to the liver. 

Von Eckardstein, A., Nofer, J.R., and Assmann, G., 2001, High density lipoproteins and arteriosclerosis. Role of cholesterol efflux and reverse cholesterol transport, Arterioscler. Thromb. Vase. Biol. 21 13-27. 

The quantity of cholesterol transported from the liver to peripheral tissues greatly exceeds its catabolism there and mechanisms exist to return cholesterol to the liver. Through this reverse transport, cholesterol is carried by high-density lipoprotein (HDL) from peripheral cells to the liver where it is taken up by a process involving hepatic lipase. Cholesterol in the plasma is also recycled to LDL and VLDL by cholesterol-ester transport protein (CETP). 

Figure 26-21 Reverse cholesterol transport pathway. HDl High-density lipoproteins LDL, low-density lipoproteins tDL, intermediate-density lipoproteins HTL, hepatic lipoprotein lipase LCAT, lecithin cholesterol acyltransferase CETP, cholesteryl ester transfer protein apo E, apoiipoprotein E. Cholesterol is removed from macrophages and other arterial wall cells by an HDL-mediated process. The LCAT esterifies the cholesterol content of HDL to prevent it from reentering the ceils. Cholesterol esters are delivered to the liver by one of three pathways ( ) cholesterol esters are transferred from HDL to LDL by CETP and enter the liver through the specific LDL receptor pathway (2) cholesterol esters are selectively taken from HDL by HDL receptors and HDL particles are returned to circulation for further transport or (3) HDL have accumulated apo E and therefore the particles can enter the liver through remnant receptors, (From Gwynne JT. High density lipoprotein cholesterol levels as a marker of reverse cho/estero/ tronsport./ m j Cardiol I989 64 10G-I7G. Copyright 1989, with permission from Excerpta Medico Inc.)...

GWynne JT. High-density lipoprotein cholesterol levels as a marker of reverse cholesterol transport. 

Yazdanyar A, Yeang C, Jiang XC (2011) Role of phospholipid transfer protein in high-density lipoprotein-mediated reverse cholesterol transport. Curr Atheroscler Rep 13 242-248... 

Navab M, Anantharamaiah GM, Reddy ST, et al. (2004a) Oral D-4F causes formation of pre-beta high-density lipoprotein and improves high-density Upoprotein-mediated cholesterol efflux and reverse cholesterol transport from macrophages in apolipoprotein E-null mice. Circulation 109 3215-3220... 

Nakamura Y., Kotite, L., Gan, Y., Spencer, T.A., Fielding C.J., Fielding P.E. 2004. Molecular mechanism of reverse cholesterol transport reaction of prebeta-migrating high density lipoprotein with plasma lecithin cholesterol acyltransferase. Biochemistry 43 14811-14820. 

There are two pieces of evidence in the literature that support the prediction that the cholesterol content of tissue membranes of children with SCD is increased relative to children without this hematological disease, and both are related to the phenomenon of reverse cholesterol transport, which allows the liver to eliminate excess cholesterol in peripheral tissues. Central to the reverse cholesterol transport is the efflux of cholesterol from the membranes followed by the lecithin-cholesterol acyltransferase-catalyzed acylation of that cholesterol with a fatty acid from phosphatidylcholine. This reaction is activated by high density lipoprotein (HDL) and is favored by n-3 PUFA in the HDL particles. The cholesterol esters are finally delivered to the liver bound to low density lipoprotein or by very low density Hpoproteins. 

Toth PP. Reverse cholesterol transport high-density lipoprotein s magnificent mile. Curr Atheroscler Rep 2003 5 386-393. 

All lipoprotein classes contain proteins, free and esterified cholesterol, TG and phospholipids however, the relative proportion of any component varies so that protein and phospholipid percentages are higher in a-lipoproteins (high-density lipoproteins) and lower in chylomicrons. The reverse is true for TG, while cholesterol circulates mainly as -lipoprotein (low-density lipoprotein). Since lipids circulate as lipoproteins, hyperlipaemias can be more properly defined as hyper-lipoproteinaemias. A classification of human hyperlipoproteinaemias based on chemical determination of plasma lipid classes as well as on paper electrophoretic separation of plasma lipoproteins has been proposed... 

HDL High density lipoprotein carries about 20% of plasma cholesterol. Its levels negatively correlate with risk of coronary heart disease. Is thought to mediate reverse cholesterol transport. ... 

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