Targeting HDL-mediated cellular cholesterol efflux for the treatment and prevention of atherosclerosis

The hallmark of the atherosclerotic lesion is the overaccumulation of chole sterol in arterial wall cells. As no pathway exists for the degradation of cholesterol in peripheral cells, a mechanism is necessary to prevent its ac cumulation to toxic levels in these cells and to allow its delivery to the liver for excretion in bile. Promoting this reverse cholesterol transport p athway is believed to be the main cardioprotective action of high density L ipoprotein (HDL). The rate-limiting step in this pathway is likely the init ial removal of cholesterol from peripheral cells by HDL. The pathway HDL ut ilizes for inducing efflux of excess cellular cholesterol represents an imp ortant and as-yet untapped mechanism to employ for the treatment and preven tion of atherosclerotic vascular disease. This review summarizes the potent ial cardioprotective actions of HDL, the mechanisms of HDL-mediated cellula r cholesterol efflux, and evidence that the specific pathway of cholesterol removal by HDL may be enhanced and used as a novel target in the therapy o f atherosclerosis. (C) 1999 Elsevier Science B.V. All rights reserved.