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Summary: Journal of Lipid Research Volume 42, 2001 1717
Pivotal role of ABCA1 in reverse cholesterol
transport influencing HDL levels and susceptibility
to atherosclerosis
Alan D. Attie,* John P. Kastelein, and Michael R. Hayden1,§
Departments of Biochemistry and Comparative Biosciences,* University of Wisconsin-Madison, Madison, WI
53706; Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands; and
Centre for Molecular Medicine and Therapeutics,§ University of British Columbia, 980 West 28th Avenue,
Vancouver, BC V5Z 4H4, Canada; and Xenon Genetics, Inc., Vancouver BC, Canada V6T 1Z3
Abstract The identification of mutations in ABCA1 in pa-
tients with Tangier disease and familial HDL deficiency
demonstrated that inadequate transport of phospholipid
and cholesterol to the extracellular space results in the hy-
percatabolism of lipid-poor nascent HDL particles. How-
ever, the relationship between changes in ABCA1 activity
and HDL levels is not clear. To address this question di-
rectly in vivo, we have used bacterial artificial chromosome
transgenic approaches, which allow for appropriate devel-
opmental and cellular localization of human ABCA1 in
mouse tissues. Increased expression of ABCA1 is directly
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