Rate-limiting factors of cholesterol efflux in reverse cholesterol transport: acceptors and donors.

1. Plasma levels of high-density lipoprotein (HDL) are believed to be inversely related to coronary artery disease. High-density lipoprotein plays a key role in the process of reverse cholesterol transport, by which HDL is able to extract excess cholesterol from peripheral tissues and transfer it to the liver for biliary excretion. 2. Efflux of lipids (cholesterol and phospholipids) is the first step in reverse cholesterol transport. Several cellular membrane transporters, including ABCA1 and ABCG1, as well as scavenger receptor (SR)-BI receptor, are believed to facilitate the active efflux of cholesterol to lipid-poor apolipoprotein A-I and mature HDL, respectively. Furthermore, overexpression or deletion of one or more specific genes supports the view that HDL is involved in cholesterol efflux. 3. In conclusion, current evidence supports a critical role for HDL in atheroprotection via an active efflux pathway through reverse cholesterol transport, with the substantial support of appropriate functions of cell donors.