Mechanisms of atherogenesis

Recently the nature of the cellular and molecular events in atherogenesis have been elucidated better. Some of these findings may be important in explaining individual differences in susceptibility to atherosclerosis that are independent of known risk factors. Nonhuman primates are valuable models for the study of mechanisms of diet-induced atherosclerosis. Cynomolgus macaques are useful for studies of male-female differences in atherosclerosis, since they share with premenopausal white women a relative protection against coronary atherosclerosis compared with males. These animals are also useful for psychosocial atherosclerosis research since social status affects the extent of atherosclerosis, and experimentally induced social stress increases extent of coronary artery atherosclerosis. Nonhuman primates have also been useful for studies of individual differences in susceptibility to diet-induced atherosclerosis and its risk factors. These studies have indicated that about 75% of the variability in the plasma cholesterol response to dietary cholesterol is attributable to genetically determined differences in cholesterol absorption and lipoprotein catabolism. There is preliminary evidence suggesting the existence of "mesenchymal susceptibility" in nonhuman primates; i.e., differences in risk of atherosclerosis that are independent of exposure to known risk factors. Efforts are being made to establish colonies of rhesus monkeys that possess contrasting degrees of mesenchymal susceptibility.