Section Review: Cardiovascular and Renal: ACAT inhibitors in development

Abstract

Acyl-CoA:cholesterol acyltransferase (ACAT), which catalyses the intracellular formation of cholesteryl esters, plays an important role in the intestinal absorption of cholesterol, foam cell formation within the arterial wall and may be very low density lipoprotein production in the liver. Therefore, the inhibition of ACAT as treatment for hypercholesterolaemia and atherosclerosis is an attractive target. Indeed, many of the ACAT inhibitors have shown potent hypocholesterolaemic and anti-atherosclerotic effects in various experimental animal models. Despite initial failures to show efficacy in humans, several ACAT inhibitors are now under clinical evaluation. The results obtained from these clinical studies should help to determine the future of ACAT inhibitors as hypocholesterolaemic and anti-atherosclerotic agents.