Cholesteryl Ester Synthesis in Normal and Atherosclerotic Aortas of Rabbits and Rhesus Monkeys

Abstract

The formation of cholesteryl ester in aortic tissue was studied using subcellular fractions from normal and atherosclerotic rabbit and rhesus monkey aortas. The properties of two enzyme systems capable of esterifying 1- 14 C-oleic acid into cholesteryl ester in vitro were investigated, and increased activity was demonstrated for both systems as a result of cholesterol feeding. Microsomal preparations were used to study the ATP, CoA-dependent esterification which involves two enzymes, fatty acyl CoA synthetase and fatty acyl CoA: cholesterol acyltransferase. The properties of both enzymes were investigated, and an increase of about fourfold in activity of the acryltransfrease was demonstrated in aortic microsomes as a result of cholesterol feeding for 3-6 months. Esterification of oleic acid into cholesteryl ester by aortic high-speed supernatant fractions at an acidic pH was also observed; the enzyme system involved did not require cofactors, and its activity greatly increased as a result of cholesterol feeding. Similar increases in the activity of both esterifying enzyme systems were found when normal and atherosclerotic rhesus monkey aortic fractions were compared. p -Chlorophenoxyisobutyrate (CPIB) and 2-methyl-2-[ p -(1, 2, 3, 4-tetrahydro-l-naphthyl)-phenoxy]propionic acid (TPIA) produced inhibition of both cholesterol-esterifying enzyme systems. TPIA was a more effective inhibitor than CPIB on both enzyme systems by at least an order of magnitude. These studies suggest that increased intracellular synthesis of cholesteryl ester by aortic tissue may contribute to its accumulation in atherosclerosis.