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Correspondence to:
John F. Oram, To whom correspondence should be addressed., joram{at}u.washington.edu (E-mail)
It is widely believed that HDL functions to transport cholesterol from peripheral cells to the liver by reverse cholesterol transport, a pathway that may protect against atherosclerosis by clearing excess cholesterol from arterial cells. A cellular ATP-binding cassette transporter (ABC) called ABCA1 mediates the first step of reverse cholesterol transport: the transfer of cellular cholesterol and phospholipids to lipid-poor apolipoproteins. Mutations in ABCA1 cause Tangier disease (TD), a severe HDL deficiency syndrome characterized by accumulation of cholesterol in tissue macrophages and prevalent atherosclerosis. Studies of TD heterozygotes revealed that ABCA1 activity is a major determinant of plasma HDL levels and susceptibility to CVD. Drugs that induce ABCA1 in mice increase clearance of cholesterol from tissues and inhibit intestinal absorption of dietary cholesterol. Multiple factors related to lipid metabolism and other processes modulate expression and tissue distribution of ABCA1.
Therefore, as the primary gatekeeper for eliminating tissue cholesterol, ABCA1 has a major impact on cellular and whole body cholesterol metabolism and is likely to play an important role in protecting against cardiovascular disease. — Oram, J. F., and R. M. Lawn. ABCA1: the gatekeeper for eliminating excess tissue cholesterol. J. Lipid Res. 2001. 42: 1173;–1179.
Supplementary key words:
HDL, reverse cholesterol transport, cellular cholesterol trafficking, cholesterol efflux, phospholipid efflux, cardiovascular disease, Tangier disease, LXR, ABCA1 gene regulation
Copyright © 2001 by Lipid Research, Inc.
Thematic Review
ABCA1: the gatekeeper for eliminating excess tissue cholesterol
John F. Orama and
Richard M. Lawnb
a Department of Medicine, Box 356426, 1959 NE Pacific Pl., University of Washington, Seattle, WA 98195-6426
b CV Therapeutics, Inc., Palo Alto, CA 94304
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