ENHANCEMENT OF AORTIC CHOLESTEROL DEPOSITION BY DIETARY LINOLEIC-ACIDIN CHOLESTEROL-FED MICE - AN ANIMAL-MODEL FOR PRIMARY SCREENING OF ANTIATHEROSCLEROTIC AGENTS

We tried to develop an experimental model using mice for the primary s creening of antiatherosclerotic agents. Male ICR strain mice were give n a high-cholesterol diet supplemented with 10% linoleic acid for 14 w eeks. Throughout the experimental period, weight gain of these mice wa s significantly inhibited as compared to that of control mice given a basal diet, but displayed a steady increase comparable to that of the high-cholesterol diet without linoleic acid. The cholesterol and linol eic acid-fed mice showed increased serum cholesterol and phospholipid levels, and decreased serum triglyceride and high-density lipoprotein- (HDL) cholesterol levels and lecithin/cholesterol acyltransferase (LCA T) activity, as well as a markedly increased lipid peroxide level whic h was a characteristic appearance in the serum of this mouse model. At the end of the experiment, uniform and significant increases in chole sterol, notably cholesteryl ester, were observed in the aorta. Also fo und were marked decreases in the aorta contents of desmosine and isode smosine, which are cross-linking amino acids present only in the elast in. Histological observations showed accumulations of fatty droplets i n the intima. These changes were much less in mice receiving a high-ch olesterol diet without linoleic acid. In this mouse model, probucol pr evented elevation of serum cholesterol, phospholipid, and cholesterol accumulation in the aorta. Increases in lipid peroxide level and decre ases in LCAT activity were also prevented. These findings indicate tha t this mouse model is useful for primary screening of antiatherosclero tic agents with antioxidative activity.