Therapeutic potential of ACAT inhibitors as lipid lowering and anti-atherosclerotic agents.
Hypercholesterolemia is one of the few independent risk factors definitively linked to increased morbidity and mortality due to myocardial infarction. One possible therapy of current interest is the prevention of the absorption of dietary cholesterol by inhibiting the enzyme, acyl-CoA: cholesterol acyltransferase (ACAT), which catalyses the intracellular formation of cholesterol esters. Evidence is now accumulating that suggests that ACAT inhibition may not only lower plasma cholesterol levels, but may also have a direct effect at the artery wall, where ACAT has been shown to be responsible for the accumulation of cholesterol esters in arterial lesions. Drago Sliskovic and Andrew White discuss the importance of ACAT in the lipid transport system and the consequences of its inhibition in a variety of tissues, with emphasis on both lipid-lowering and anti-atherosclerotic effects.
Sliskovic
D R
DR
Department of Chemistry, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, MI 48105.
White
A D
AD
D000818:Animals; D001161:Arteriosclerosis / Q000188:drug therapy*; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008099:Liver / Q000201:enzymology; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors*
D000960:Hypolipidemic Agents; D002785:Sterol O-Acyltransferase