Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:720-727
Published online before print January 9, 2003, doi: 10.1161/01.ATV.0000054662.44688.9A
Published online before print January 9, 2003, doi: 10.1161/01.ATV.0000054662.44688.9A
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© 2003 American Heart Association, Inc.
ATVB In Focus |
HDL Apolipoproteins and ABCA1
Partners in the Removal of Excess Cellular Cholesterol
From the Department of Medicine, University of Washington, Seattle.
Correspondence to John F. Oram, Department of Medicine, Box 356426, University of Washington, Seattle, WA 98195. E-mail joram{at}u.washington.edu
It is widely believed that HDL protects against atherosclerosis by removing excess cholesterol from arterial cells. Lipid-poor HDL apolipoproteins promote efflux of cholesterol, phospholipids, and other lipophilic molecules from cells by an active process mediated by a cell-membrane transporter called the ATP binding cassette transporter A-1 (ABCA1). ABCA1 either directly or indirectly translocates phospholipids and cholesterol to the cell surface, where they appear to form lipid domains that interact with amphipathic 
-helixes in apolipoproteins. This interaction solubilizes these lipids and generates nascent HDL particles that dissociate from the cell. Binding of apolipoproteins to ABCA1 may also enhance the activity of this lipid-transport pathway. Thus, the apolipoprotein/ABCA1 pathway efficiently clears cells of excess cholesterol that would otherwise accumulate as intracellular lipid droplets. ABCA1 expression is highly induced by cholesterol loading of cells and is also modulated by sterol-independent mechanisms at both the transcriptional and posttranslational level. Studies of human disease and animal models have shown that both an increased availability of apolipoproteins and an enhanced macrophage ABCA1 activity are atheroprotective. These findings implicate the apolipoprotein/ABCA1 pathway as an important therapeutic target for treating cardiovascular disease.
Key Words: HDL • apolipoproteins • ABCA1 • cholesterol efflux • cardiovascular disease
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