Diet-Induced Atherosclerosis in Cynomolgus Monkey Aorta and Regression by the Sixth-Month Observation

Abstract

Pathomorphologic analysis was employed to evaluate diet-induced athero sclerosis in cynomolgus monkey aorta and regression by administration of a hypolipidemic agent for six months after the atherogenic ration. Twenty-seven male cynomolgus monkeys were divided into three groups. Group A was fed individually with a high-fat diet containing 0.3% cholesterol under identical conditions for six months. Group B was fed with normal monkey chow for six months after the same atherogenic ration. Group C was fed with normal mon key chow and administered a hypolipidemic agent 1% of 4-[2-(4-isopropylben zamido)ethoxy] benzonic acid for six months after the same atherogenic ration. Each thoracic and abdominal aorta of animal models was separately analyzed. Lipid composition analysis and esterified cholesterol (CE) in aortic wall, ratio of free cholesterol to phospholipid, surface involvement, and atherosclerotic index after Sudan IV staining were studied for evaluation of progression and regres sion. The configurations of atherosclerotic involvement were histologically eval uated among each group. These observed lesions, features specific to cynomol gus lesions, mainly consisted of lipid-rich foam cells, lipid debris, and prolifer ated extracellular matrix. No different lesion composition was noted between the thoracic and abdominal aorta. This may suggest that some local factors play an important role for development of atherosclerosis after the initial event. Group C had remarkable reduction of foam cells and of CE accumulation in both the thoracic and abdominal aortic wall. Accelerated regression in group C as compared with group B was demonstrated both biochemically and pathohis tologically. These results suggest that substantial regression of atherosclerosis in both the thoracic and abdominal aorta can be expected. This hypolipidemic agent exerts notable antiatherosclerotic activity, along with a lowering effect on plasma total cholesterol levels.