Reverse cholesterol transport and atherosclerosis. A mini review.
Reverse cholesterol transport (RCT) is a complex process ensuring the efflux of cholesterol from peripheral cells and its transport back in the liver for its metabolism and biliary excretion. Cholesterol efflux results by the interaction of a cellular free cholesterol and phospholipid transporter, the ABC-AI, with lipid poor apoAI, endowed HDL particles. The free cholesterol taken up by HDL is then esterified by lecithin:cholesterol acyltransferase (LCAT) and the hydrophobic cholesteryl esters are retained into the core of HDL, so that new cholesterol molecules can be translocated on the HDL surface. The generated cholesteryl esters are partially transferred to triglyceride rich apoB containing lipoprotein through a nonenzymatic process mediated by cholesteryl ester transfer protein (CETP) in exchange for triglyceride. The hepatic uptake of the cholesterol released from peripheral cells may thus proceed via an HDL-receptor, the SR-BI and through the LDL receptor route. Hepatic lipase (HL) facilitates the selective uptake of cholesteryl esters by the hepatocytes by exerting a lipolytic effect and a ligand-binding effect, bridging the lipoprotein particles to the heparan sulfate proteoglycans on cells surface and allowing the transcytosis of cholesteryl esters. Studies on genetically modified animals and on humans with severe genetic deficiencies demonstrated that abnormalities of the various components of RCT would accelerate atherogenesis. Clinical studies revealed that the development of coronary artery disease (CAD) may by delayed by increased HL activity in patients with familial hypercholesterolemia (heterozygotes), while in hypertriglyceridemic patients an increased plasma CETP and HL levels would favor the generation of less lipidated HDL and of small dense atherogenic LDL particles.
Cucuianu
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Clinical Center of Diabetes Nutrition and Metabolic Diseases, Cluj-Napoca, Romania.
Coca
Mariana
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Hâncu
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D050197:Atherosclerosis / Q000209:etiology* / Q000378:metabolism; D001692:Biological Transport / Q000502:physiology*; D002784:Cholesterol / Q000378:metabolism*; D006801:Humans; D008099:Liver / Q000378:metabolism
D002784:Cholesterol