Four
adenosine triphosphate-binding cassette (ABC) transporters-ABCA1, ABCG1, ABCG5, and ABCG8-have been identified and shown to modulate
cholesterol and
lipoprotein metabolism. Recent analyses of ABCA1 indicate that upregulation of ABCA1 in the liver and macrophages of transgenic mice is associated with increased plasma
high-density lipoprotein (
HDL) cholesterol levels, increased net flux of
cholesterol to the liver, and reduced diet-induced
atherosclerosis. In ABCA1 transgenic mice, the enhanced expression of hepatic ABCA1 transporters is associated with increased plasma
HDL cholesterol levels, suggesting that the liver plays an important role in the levels of plasma
HDL cholesterol. Overexpression of ABCG1 in the liver of mice using recombinant ABCG1 vectors results in decreased plasma HDL levels and indicates that ABCG1 can modulate plasma
lipoprotein levels in vivo. The potential importance of ABCG1 in reverse
cholesterol transport has not been definitively established. Studies in patients with
sitosterolemia have identified 2 major new transporters, ABCG5 and ABCG8, that play a pivotal role in the regulation of intestinal
cholesterol, plant, and shellfish absorption. Modulation of the expression of ABCG5 and ABCG8 represents an important new mechanism in the regulation of
cholesterol absorption in the intestine. The
ABC transporters currently represent excellent targets for the development of new drugs for the treatment of patients with increased risk of premature
cardiovascular disease.