Dietary Mitigation of Psychosocial Stress Effects on CVD Risk

描述（由申请人提供）：心血管疾病（CVD）是女性死亡和残疾的主要原因。心理社会压力增加女性和雌性食蟹猴的心血管疾病和心血管疾病风险因素，并导致抑郁症和卵巢功能障碍，这是女性特别重要的心血管疾病风险因素。影响心血管健康的环境刺激最初由大脑处理，大脑对营养敏感，调节心血管功能， 下游的压力敏感系统，并可能在CVD患者的结构不同。重要的是，大多数证明压力对CVD影响的数据都来自食用西方饮食的受试者。相比之下，谨慎的饮食消费与抑郁症，不孕症，传统CVD危险因素和CVD的风险降低有关。新出现的实验数据表明，西方饮食的某些特征加剧了生理和行为应激反应，这些急性效应反映了西方饮食消费与人口研究中感知的压力之间的联系。因此，心理社会压力对CVD/CAA风险的影响可能不仅仅是压力的主要影响;它们可能反映了饮食加剧的压力反应。在这里，我们建议测试的假设，心理社会压力相关的心血管疾病的风险是由于部分西方饮食加剧的压力反应，因此，消费谨慎的饮食将减少生理压力反应，减轻有害影响的心理社会压力对心血管疾病的风险。将在基线时以及西方或谨慎饮食18和36个月后，在成年雌性猴中评估应激和抑郁的行为和生理指标、摄食量和活动水平、CVD风险因素、身体组成、组织基因表达以及关键神经区域的体积和其他测量。将在髂动脉、颈动脉和冠状动脉中测量动脉粥样硬化。目的是确定西方和谨慎饮食对以下方面的影响：1）对急性应激源的生理反应，2）慢性应激的生理和行为指标，3）CVD风险，动脉粥样硬化和动脉基因表达，以及4）社会应激的从属和主导猴子的关键神经区域的结构特征。与人类研究相比，这是对饮食的行为、生理和病理影响的更具侵入性和详细的研究，并且来自该模型的数据比其他动物模型更适合临床转化。如果成功，拟议的研究将证明谨慎饮食可以减轻心理社会压力对CVD风险的一些有害影响，从而提供一种具有广泛疗效的心理压力干预措施。

DESCRIPTION (provided by applicant): 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.