Managing the risk of atherosclerosis: the role of high-density lipoprotein

The association of low levels of high-density lipoprotein cholesterol (HDL-C) with an increased incidence of cardiovascular events implies a central involvement of high-density lipoprotein (HDL) in the retardation of the atherosclerotic process and the corresponding slowing of progression of coronary artery disease. HDL-C appears to exert this protective effect through multiple mechanisms. Through its association with antioxidant enzymes, such as paraoxonase and the platelet-activating factor acetylhydrolase, it may protect low-density lipoprotein (LDL) from oxidation and decrease the expression of adhesion molecules, both of which contribute importantly to the initiation of atherosclerotic plaques. HDL may also further inhibit plaque expansion by improving the stability of existing plaques, and it may reduce the susceptibility of plaques to rupture by mediating reverse cholesterol transport. This article examines recent experimental approaches aimed at elucidating these antiatherogenic, HDL-mediated mechanisms.