Social Environment Influences the Progression of Atherosclerosis in the Watanabe Heritable Hyperlipidemic Rabbit

Abstract

Background — Although there is evidence that emotionally stressful behavior can accelerate the progression of atherosclerosis, there is less data to support the notion that affiliative social behavior can slow disease progression. The present study examines the influence of social environment on the progression of atherosclerosis in the Watanabe Heritable Hyperlipidemic (WHHL) rabbit, a model that spontaneously develops lesions because of a genetic defect in lipoprotein clearance. Methods and Results — WHHL rabbits were assigned to 1 of 3 social or behavioral groups: an unstable group, in which unfamiliar rabbits were paired daily, with the pairing switched each week; a stable group, in which littermates were paired daily for the entire study; and an individually caged group. The stable group exhibited more affiliative social behavior and less agonistic behavior than the unstable group and significantly less aortic atherosclerosis than each of the other 2 groups. Although the unstable and individually caged groups had comparable aortic lesion areas, the severity of the disease progressed faster in the unstable group, as indexed by a larger area of calcification and increased fibrous cap thickness in complex lesions. The unstable group showed increased agonistic behavior and signs of chronic adrenocortical and gonadal activation, whereas the individually caged group was relatively sedentary, had low glucocorticoid levels, and was hyperinsulinemic compared with the other groups. Conclusions — The present study demonstrates that social environment can slow, as well as accelerate, the progression of atherosclerosis. It also emphasizes the importance of behavioral factors in atherogenesis, even in a model of disease with strong genetic determinants.