Monkeys, aggression, and the pathobiology of atherosclerosis

Although it is frequently hypothesized that psychosocial factors influence the development of coronary heart disease and the underlying atherosclerosis, evidence directly supporting this hypothesis or identifying the mediating mechanisms has been sparse at best. The present article reviews research designed to elucidate the role of behavior in the pathogenesis of atherosclerosis (and thus coronary heart disease). Particular emphasis is placed on experimental evidence linking atherosclerosis to both behavior and sympathoadrenal activation in cynomolgus macaques (Macaca fascicularis). In males of this monkey species, behavioral dominance and aggression interact with social instability to promote the development of diet-induced atherosclerosis. Beta-adrenoreceptor blockade prevents this behavioral exacerbation of atherosclerosis, suggesting a mechanism of sympathetic origin. Furthermore, independently of social rank or environmental perturbation, animals exhibiting a heightened cardiac responsivity to stress are excessively aggressive and also develop the most extensive coronary lesions. Taken together, these experimental data strongly implicate aggressiveness and sympathetic arousal, occurring as a result of either inherent hypersensitivity or environmental stimulation, in the pathogenesis of atherosclerosis. Additional data suggest that a specific neurotransmitter complex-the serotonergic (5-hydroxytryptamine) system-modulates factors associated with the expression of social dominance and exaggerated heart rate reactivity, perhaps thereby explaining a portion of variable susceptibility to atherosclerosis and coronary heart disease.