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

Abstract

Pathomorphologic analysis was employed to evaluate diet-induced atherosclerosis 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 monkey chow and administered a hypolipidemic agent 1% of 4-[2-(4-isopropylbenzamido)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 regression. The configurations of atherosclerotic involvement were histologically evaluated among each group. These observed lesions, features specific to cynomolgus lesions, mainly consisted of lipid-rich foam cells, lipid debris, and proliferated 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 pathohistologically. 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.

Comparison of Lipoprotein Separation and Lipid Analysis Methodologies for Human and Cynomolgus Monkey Plasma Samples

“…There has been increased interest in using cynomolgus monkeys as a preclinical animal model for lipoprotein research and studying atherosclerosis, as they showed more human-like diet-induced dyslipidemia and atherogenesis than other preclinical animal models [22][23][24][25]. We therefore included cynomolgus plasma samples in our study, to determine whether the commonly used methods for lipoprotein and lipid analysis, mainly targeted for human subjects, could be applied for quantitative analysis of lipids in a non-human primate.…”