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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:1755.)
© 2004 American Heart Association, Inc.

Brief Reviews

Regulation of Plasma High-Density Lipoprotein Levels by the ABCA1 Transporter and the Emerging Role of High-Density Lipoprotein in the Treatment of Cardiovascular Disease

H. Bryan Brewer, Jr; Alan T. Remaley; Edward B. Neufeld; Federica Basso; Charles Joyce

From the Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md.

Correspondence to H. Bryan Brewer, Jr, Molecular Disease Branch, NHLBI, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892. E-mail bryan{at}mdb.nhlbi.nih.gov

High-density lipoproteins (HDL) protect against cardiovascular disease. HDL removes and transports excess cholesterol from peripheral cells to the liver for removal from the body. HDL also protects low-density lipoproteins (LDL) from oxidation and inhibits expression of adhesion molecules in endothelial cells, preventing monocyte movement into the vessel wall. The ABCA1 transporter regulates intracellular cholesterol levels in the liver and in peripheral cells by effluxing excess cholesterol to lipid-poor apoA-I to form nascent HDL, which is converted to mature -HDL by esterification of cholesterol to cholesteryl esters (CE) by lecithin cholesterol acyltransferase. The hepatic ABCA1 transporter and apoA-I are major determinants of levels of plasma -HDL cholesterol as well as poorly lipidated apoA-I, which interact with ABCA1 transporters on peripheral cells in the process of reverse cholesterol transport. Cholesterol in HDL is transported directly back to the liver by HDL or after transfer of CE by the cholesteryl ester transfer protein (CETP) by the apoB lipoproteins. Current approaches to increasing HDL to determine the efficacy of HDL in reducing atherosclerosis involve acute HDL therapy with infusions of apoA-I or apoA-I mimetic peptides and chronic long-term therapy with selective agents to increase HDL, including CETP inhibitors.

High-density lipoproteins (HDL) protect against cardiovascular disease. Current approaches to increasing HDL to determine its efficacy in reducing atherosclerosis involve acute HDL therapy with infusions of apoA-I or apoA-I mimetic peptides and chronic long-term therapy with selective agents to increase HDL, including CETP inhibitors.

Key Words: ABCA1 transporter • cholesterol • cholesteryl ester transfer protein • cholesteryl ester transfer protein inhibitor • apoA-I

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