HEPATIC ORIGIN OF CHOLESTERYL OLEATE IN CORONARY-ARTERY ATHEROSCLEROSIS IN AFRICAN-GREEN MONKEYS - ENRICHMENT BY DIETARY MONOUNSATURATED FAT

Relationships among plasma lipoprotein cholesterol, cholesterol secret ion by the isolated, perfused liver, and coronary artery atheroscleros is were examined in African green monkeys fed diets containing cholest erol and 35% of calories as fat enriched in polyunsaturated, monounsat urated, or saturated fatty acids, The livers of animals fed monounsatu rated fat had significantly higher cholesteryl ester concentrations (8 .5 mg/g wet wt) than the livers of the other diet groups (3.65 and 3.3 7 mg/g wet wt for saturated and polyunsaturated fat groups, respective ly) and this concentration was highly correlated with plasma cholester ol and apoB concentrations in each diet group, Cholesteryl oleate was 58 and 74.5% of the Liver cholesteryl ester in the saturated and monou nsaturated fat groups, in each diet group, perfusate cholesteryl ester accumulation rate was highly correlated to liver and plasma cholester ol concentrations, and to plasma LDL cholesteryl ester content, Choles teryl oleate was 48 and 67% of the cholesteryl esters that accumulated in perfusate in the saturated and monounsaturated fat animals, and th is percentage was very highly correlated (r = -0.9) with plasma apoB c oncentration, Finally, in these two diet groups, liver perfusate chole steryl ester accumulation rate was well correlated (r greater than or equal to 0.8) to coronary artery cholesteryl ester concentration, a me asure of the extent of coronary artery atherosclerosis that occurred o ver the five years of diet induction in these animals, These data defi ne an important role for the liver in the cholesteryl oleate enrichmen t of the plasma lipoproteins in the saturated and monounsaturated fat groups, and demonstrate strong relationships among hepatic cholesteryl ester concentration, cholesteryl ester secretion, and LDL particle ch olesteryl ester content, The high correlation between liver cholestery l ester secretion and coronary artery atherosclerosis provides the fir st direct demonstration of the high degree of importance of hepatic ch olesteryl ester secretion in the development of this disease process, The remarkable degree of enrichment of cholesteryl oleate in plasma ch olesteryl esters of the monounsaturated fat group may account for the relatively high amount of coronary artery atherosclerosis in this grou p.