Regulation of reverse cholesterol transport and clinical implications

Plasma levels of high-density lipoprotein (HDL) cholesterol and its major protein, apolipoprotein A-1, are inversely correlated with the incidence of atherosclerotic cardiovascular disease. Low HDL cholesterol and apolipoprotein A-1 levels often are found in association with other cardiovascular risk factors, including the metabolic syndrome, insulin resistance, and type 2 diabetes mellitus. However, overexpression of apolipoprotein A-1 in animals has been shown to reduce, progression and even induce regression of atherosclerosis, indicating that apolipoprotein A-1 is directly protective against atherosclerosis. A major mechanism by which apolipoprotein A-1 inhibits atherosclerosis may be by promoting cholesterol efflux from macrophages and returning it to the liver for excretion, a process termed reverse cholesterol transport. This article focuses on new developments in the regulation of reverse cholesterol transport and the clinical implications of those developments. (C) 2003 by Excerpta Medical, Inc.