New insights into the regulation of cellular cholesterol efflux and high-density lipoprotein metabolism

HIgh-denisty lipoprotein (HDL) plays a key role in the process of reverse cholesterol transport, in which it promotes cholesterol efflux from peripheral tissues and returns it to the liver for biliary excretion. The discovery of the binding cassette transporter A1 (ABCA1) has altered our understanding of the pathophysiology of cholesterol efflux and observation of patients with Tangier disease, and studies focussing on ABCA1 have demonstrated that the most critical step in HDL-biogenesis is cellular cholesterol release. ABCA1 is a rate-limiting factor for HDL assembly and is regulated by transcriptional and post-transcriptional factors. There is accumulating evidence that other molecules, such as ABCG1 and scavenger receptor class B type I, also play a pivotal role in cholesterol efflux and HDL metabolism. An advanced understanding of cholesterol efflux and HDL metabolism will facilitate the development of novel therapeutic strategies for raising plasma HDL levels and promoting reverse cholesterol transport, which should lead to new strategies for the prevention of atherosclerosis.