Role of cholesteryl ester hydrolase in atherosclerosis

Hydrolysis of cellular cholesteryl esters by neutral cholesteryl esters hydrolase (CEH) is the obligatory first step in removal of cholesterol from artery wall-associated macrophage foam cells and is increasingly being recognized as the rate-limiting step in the process of reverse cholesterol transport, by which excess cholesterol is ultimately removed from the body. In this review, we recapitulate the earlier controversies surrounding the identity of neutral CEH in macrophages, characterization of several potential candidates and their role in atherogenesis. Since final elimination of cholesterol occurs either as direct secretion into bile or as bile acids that are removed in the feces and the liver represents the major organ responsible for this final elimination, the role of hepatic CEH in the process of reverse cholesterol transport is also summarized. Neutral CEH is identified as a potential antiatherosclerotic target and future directions to manipulate CEH as a means to attenuate atherosclerosis are discussed.