Targeting HDL-mediated cellular cholesterol efflux for the treatment and prevention of atherosclerosis.
The hallmark of the atherosclerotic lesion is the overaccumulation of cholesterol in arterial wall cells. As no pathway exists for the degradation of cholesterol in peripheral cells, a mechanism is necessary to prevent its accumulation to toxic levels in these cells and to allow its delivery to the liver for excretion in bile. Promoting this reverse cholesterol transport pathway is believed to be the main cardioprotective action of high density lipoprotein (HDL). The rate-limiting step in this pathway is likely the initial removal of cholesterol from peripheral cells by HDL. The pathway HDL utilizes for inducing efflux of excess cellular cholesterol represents an important and as-yet untapped mechanism to employ for the treatment and prevention of atherosclerotic vascular disease. This review summarizes the potential cardioprotective actions of HDL, the mechanisms of HDL-mediated cellular 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 of atherosclerosis.
Francis
G A
GA
Department of Medicine, University of Alberta, Edmonton, Canada. gordon.francis@ualberta.ca
Perry
R J
RJ
D001161:Arteriosclerosis / Q000188:drug therapy* / Q000517:prevention & control*; D001692:Biological Transport; D002784:Cholesterol / Q000378:metabolism*; D005609:Free Radicals; D006801:Humans; D008075:Lipoproteins, HDL / Q000502:physiology*; D010084:Oxidation-Reduction; D014443:Tyrosine / Q000378:metabolism
D005609:Free Radicals; D008075:Lipoproteins, HDL; D014443:Tyrosine; D002784:Cholesterol