on January 2, 2003
Published online before print January 2, 2003, doi: 10.1161/01.ATV.0000055194.85073.FF
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Submitted on September 26, 2002
Accepted on December 5, 2002
Study of ABCA1 Function in Transgenic Mice
Charles Joyce *;
From the Molecular Disease Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Md.
* To whom correspondence should be addressed. E-mail: cjoyce{at}mail.nih.gov.
Abstract—The ATP-binding cassette transporter A1 (ABCA1), identified in 1999 as the gene defective in Tangier disease, promotes efflux of cellular cholesterol from macrophages and other peripheral tissues to apolipoprotein acceptors. These ABCA1-mediated processes are anticipated to have antiatherogenic properties, prompting the development of pharmacological agents that increase ABCA1 gene expression as well as the establishment of ABCA1-transgenic mouse lines. Preliminary studies of ABCA1-Tg mice seem to validate the selection of this transporter as a therapeutic target for the treatment of low HDL syndromes and cardiovascular disease but have also raised new questions regarding the function of ABCA1. In particular, the relative contribution of hepatic and peripheral ABCA1 to plasma HDL levels and to reverse cholesterol transport, as well as the potential role of ABCA1 in modulating the plasma concentrations of the apolipoprotein B-containing lipoproteins and protecting against atherosclerosis, seem to be promising areas of investigation. The present review summarizes the most recent studies and discusses insights provided by these transgenic mouse models.
Key words: high-density lipoproteins • apolipoprotein B-containing lipoproteins • atherosclerosis • cholesterol efflux • aortic atherosclerosis • ABC transporters
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