Cardiovascular disease (CVD) is the leading cause of death and disability in women. Psychosocial stress increases CVD and CVD risk factors in women and female cynomolgus monkeys, and leads to depression and ovarian dysfunction which are especially important CVD risk factors for women. Environmental stimuli that affect CV health are initially processed by the brain which is nutrition-sensitive, modulates the function of downstream stress-sensitive systems, and may be structurally different in CVD patients. Importantly, most of the data demonstrating stress effects on CVD have been derived from subjects consuming a Western diet. In contrast, prudent diet consumption is associated with decreases in risk of depression, infertility, traditional CVD risk factors, and CVD. Emerging experimental data suggest that certain characteristics of a Western diet exacerbate physiological and behavioral stress responses, and these acute effects reflect associations linking Western diet consumption with perceived stress in population studies. Thus, psychosocial stress effects on CVD/CAA risk may not be simply main effects of stress; they may reflect diet-exacerbated stress reactivity. Here we propose to test the hypothesis that psychosocial stress-associated CVD risk is due in part to Western diet exacerbation of stress reactivity; therefore, consumption of a Prudent diet will reduce physiological stress reactivity an mitigate the deleterious effects of psychosocial stress on CVD risk. Behavioral and physiological indicators of stress and depression, food consumption and activity levels, CVD risk factors, body composition, tissue gene expression, and volumetric and other measures of key neural regions will be assessed in adult female monkeys at Baseline, and after 18 and 36 months of a Western or Prudent diet. Atherosclerosis will be measured in iliac, carotid and coronary arteries. The aims are to determine the effects of Western and Prudent diets on 1) physiological responses to an acute stressor, 2) physiological and behavioral indices of chronic stress, 3) CVD risk, atherosclerosis and artery gene expression, and 4) structural characteristics of key neural regions in socially stressed subordinate and dominant monkeys. This is a more invasive and detailed investigation of behavioral, physiological, and pathological effects of diet than can be conducted in human studies and the data from this model are more amenable to clinical translation than other animal models. If successful, the proposed studies will demonstrate that a Prudent diet can ameliorate some deleterious effects of psychosocial stress on CVD risk, and thus provide a cost-effective intervention on psychological stress with the promise of wide-spread efficacy.

R01HL087103

2006-12-01

2020-03-31