PHYSTOESTROGENS, STRESS AND ATHEROSCLEROSIS in Females

女性的植物雌激素、压力和动脉粥样硬化

• 批准号: 6874481
• 负责人: Jay Ross Kaplan
• 金额: $ 48.52万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-04-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6874481
• 关键词: Macaca fascicularis; age difference; alternative medicine; atherosclerosis; behavioral /social science research tag; cardiovascular disorder prevention; chemoprevention; cytoprotection; diet therapy; dietary supplements; disease /disorder model; female; menstrual cycle; nonhuman therapy evaluation; nutrition related tag; pathologic process; phytoestrogens; psychological stressor; soybeans

(Adapted from Applicant's Abstract) Premenopausal women are usually thought to be protected from atherosclerosis and the resulting coronary heart disease (CHD). However, current data support the hypothesis that the atherosclerosis and clinical events observed among postmenopausal women have their origins in the premenopausal years. Related data suggest, further, that a history of clinical or subclinical ovarian impairment (the latter which may be relatively common) increases the risk for CHD. Premenopausal cynomolgus monkeys provide a periclinical surrogate for reproductive-aged women for the study of atherogenesis. In this model, the stress associated with social subordination induces ovarian dysfunction and estrogen deficiency, potentiates atherogenesis, and impairs coronary artery vasodilator responses. Treatment of socially subordinate (i.e. high risk) females with exogenous estrogen inhibits atherogenesis and improves dilator responses. The overall objective of the current study is to determine whether soy phytoestrogens (SPEs) might act as tissue-specific estrogen agonists to be similarly protective in high risk females (and by extrapolation, premenopausal women) without adverse effects on other tissues. Accordingly, 96 monkeys housed in social groups of six animals each will be divided into two treatment conditions; half the animals will receive a soy- and casein-based diet that contains SPEs while the rest will consume a soy- and casein-based diet from which SPEs have been extracted. Additionally, the social housing will place half of the animals, the subordinates, at high risk for ovarian impairment and atherosclerosis. This comprehensive, periclinical study will determine whether treatment with SPEs inhibits the progression of coronary and carotid artery atherosclerosis and improves coronary artery dilator responses in high risk, subordinate premenopausal monkeys. Furthermore, the study will determine whether SPEs inhibit or potentiate proliferation and estrogenic responses in the endometrium and mammary tissue of premenopausal monkeys, and whether SPEs adversely affect or improve bone development and peak bone mass in these females. Finally, the study will determine whether SPEs influence menstrual cyclicity or any aspect of the reproductive endocrine profile. In summary, the experiment will provide evidence concerning the use of SPE treatment as a natural, safe, nonpharmacologic intervention directed toward primary prevention of atherosclerosis in women.

绝经前妇女通常被认为是免受动脉粥样硬化和由此产生的冠心病（CHD）的影响。 然而，目前的数据支持这样的假设，即绝经后妇女中观察到的动脉粥样硬化和临床事件起源于绝经前。 相关数据进一步表明，临床或亚临床卵巢损害史（后者可能相对常见）增加了CHD的风险。 绝经前食蟹猴为育龄妇女提供了动脉粥样硬化研究的临床替代物。 在这个模型中，与社会从属关系相关的压力诱导卵巢功能障碍和雌激素缺乏，增强动脉粥样硬化形成，并损害冠状动脉血管舒张反应。 用外源性雌激素治疗社会地位低下（即高风险）的女性可抑制动脉粥样硬化形成并改善扩张反应。 本研究的总体目标是确定大豆植物雌激素（SPE）是否可以作为组织特异性雌激素激动剂，对高危女性（外推，绝经前女性）具有类似的保护作用，而对其他组织无不良影响。 因此，将96只猴子分为两种治疗条件，其中一半动物将接受含有SPE的大豆和酪蛋白饮食，而其余动物将食用提取SPE的大豆和酪蛋白饮食。 此外，社会住房将把一半的动物，下属，在卵巢功能障碍和动脉粥样硬化的高风险。 这项全面的临床前研究将确定SPE治疗是否抑制冠状动脉和颈动脉粥样硬化的进展，并改善高风险、从属的绝经前猴的冠状动脉扩张反应。此外，该研究将确定SPE是否抑制或增强绝经前猴子宫内膜和乳腺组织的增殖和雌激素反应，以及SPE是否对这些雌性动物的骨发育和峰值骨量产生不利影响或改善。 最后，这项研究将确定SPEs是否影响月经周期或生殖内分泌特征的任何方面。 总之，该实验将提供关于SPE治疗作为一种天然、安全、非药物干预用于女性动脉粥样硬化一级预防的证据。