Hepatic ACAT activity in African green monkeys is highly correlated to plasma LDL cholesteryl ester enrichment and coronary artery atherosclerosis.
Previous studies and this study of African green monkeys show a strong positive correlation between plasma low density lipoprotein (LDL) size and the extent of coronary artery atherosclerosis (CAA). Increased LDL size was principally due to the accumulation of cholesteryl oleate molecules within the particle core, suggesting that many of these cholesteryl esters were of tissue origin, i.e., from the acyl-coenzyme A:cholesterol acyltransferase (ACAT) reaction instead of the lecithin:cholesterol acyl-transferase (LCAT) reaction. The current study was conducted to test the hypothesis that ACAT in the liver is the source of the increased numbers of cholesteryl oleate molecules in plasma LDL particles that appear to increase the atherogenic potential of LDL. Monkeys were fed diets rich in fat (lard, safflower oil, or fish oil) and cholesterol for 3-6 years before liver perfusion, ACAT assay, and evaluation of CAA. Hepatic ACAT activity was positively correlated with hepatic cholesteryl ester secretion (r = 0.61, p < 0.001), plasma LDL cholesteryl ester content (r = 0.60, p < 0.0001), and the extent of CAA (r = 0.62, p < 0.0001). The number of cholesteryl oleate molecules within LDL increased proportionally with LDL size in each of the diet groups. Hepatic cholesteryl oleate concentration was correlated with the accumulation of cholesteryl oleate in liver perfusate (r = 0.72, p < 0.01) and with plasma LDL cholesterol oleate content (r = 0.73, p < 0.0001). Our interpretation is that these data, obtained in a relevant primate model of CAA, suggest that hepatic ACAT increases the atherogenicity of LDL by augmenting both the secretion by the liver and accumulation in plasma LDL of cholesteryl oleate.
Carr
T P
TP
Department of Comparative Medicine, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, N.C. 27157-1040.
Parks
J S
JS
Rudel
L L
LL
D000818:Animals; D002522:Chlorocebus aethiops; D002788:Cholesterol Esters / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood*; D003324:Coronary Artery Disease / Q000378:metabolism*; D005227:Fatty Acids / Q000032:analysis; D008099:Liver / Q000201:enzymology*; D008297:Male; D002785:Sterol O-Acyltransferase / Q000032:analysis*
D002788:Cholesterol Esters; D008078:Cholesterol, LDL; D005227:Fatty Acids; D002785:Sterol O-Acyltransferase