Acyl-coenzyme A:cholesterol acyltransferase inhibitors for controlling hypercholesterolemia and atherosclerosis.

Abstract Acyl-coenzyme A:cholesterol acyltransferase (ACAT; Sterol O-acyltransferase/SOAT) is an intracellular enzyme that catalyzes the formation of cholesteryl esters from cholesterol and fatty acyl-coenzyme A. ACAT inhibitors reduce plasma cholesterol levels by suppressing absorption of dietary cholesterol and by suppressing the assembly and secretion of apolipoprotein B-containing lipoproteins such as very low density lipoprotein in liver and chylomicron in intestine. Moreover, ACAT inhibitors prevent the conversion of macrophages into foam cells in the arterial walls. Thus, ACAT inhibitors are under investigation for controlling hypercholesterolemia and the development of atherosclerosis. Some potent ACAT inhibitors have been tested for their efficacy and safety in humans.