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.

Public Health Relevance

This project seeks to determine if diet exacerbates psychosocial stress effects on cardiovascular health, and to evaluate the potential for diet modification to attenuate psychosocial stress effects on cardiovascular disease in female nonhuman primates. If successful the proposed study will provide a cost-effective intervention on psychological stress with the promise of wide-spread efficacy.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL087103-10
Application #
9252507
Study Section
Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
Program Officer
Stoney, Catherine
Project Start
2006-12-01
Project End
2018-03-31
Budget Start
2017-04-01
Budget End
2018-03-31
Support Year
10
Fiscal Year
2017
Total Cost
$698,704
Indirect Cost
$226,607
Name
Wake Forest University Health Sciences
Department
Pathology
Type
Schools of Medicine
DUNS #
937727907
City
Winston-Salem
State
NC
Country
United States
Zip Code
27157
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Silverstein-Metzler, Marnie G; Shively, Carol A; Clarkson, Thomas B et al. (2016) Sertraline inhibits increases in body fat and carbohydrate dysregulation in adult female cynomolgus monkeys. Psychoneuroendocrinology 68:29-38
Kavanagh, Kylie; Brown, Richelle N; Davis, Ashley T et al. (2016) Microbial translocation and skeletal muscle in young and old vervet monkeys. Age (Dordr) 38:58
Maldjian, Joseph A; Shively, Carol A; Nader, Michael A et al. (2016) Multi-Atlas Library for Eliminating Normalization Failures in Non-Human Primates. Neuroinformatics 14:183-90
Willard, Stephanie L; Uberseder, Beth; Clark, Ashlee et al. (2015) Long term sertraline effects on neural structures in depressed and nondepressed adult female nonhuman primates. Neuropharmacology 99:369-78
Shively, Carol A; Register, Thomas C; Appt, Susan E et al. (2015) Effects of long-term sertraline treatment and depression on coronary artery atherosclerosis in premenopausal female primates. Psychosom Med 77:267-78
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Shively, Carol A; Register, Thomas C; Higley, J Dee et al. (2014) Sertraline effects on cerebrospinal fluid monoamines and species-typical socioemotional behavior of female cynomolgus monkeys. Psychopharmacology (Berl) 231:1409-16

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