Acyl coenzyme A:cholesterol acyltransferase inhibition: potential atherosclerosis therapy or springboard for other discoveries?

ABSTRACT

Cholesterol is an essential building block without which humans and other animals could not exist. As with most necessities, under certain conditions, excess can sharply tip the scale and lead to an unfavourable outcome. Excess cholesterol is stored as cholesteryl ester through an esterification process regulated in part by acyl coenzyme Acholesterol acyltransferase (ACAT). ACAT is found in many tissue types which require the storage of cholesterol. Most notably, for cardiovascular disease ACAT activity is significant in intestinal and hepatic tissue and arterial macrophages. Several ACAT inhibitors have been investigated for their potential to favourably alter serum lipoprotein levels by blocking intestinal absorption, hepatic inhibition and/or slowing the progression of atherosclerosis through a non-lipid arterial inhibition. Recent evaluations of ACAT and ACAT inhibitors have provided some insight into the therapeutic potential and risks of ACAT inhibition as a means of treating atherosclerosis.