SOY, LIFE STAGE, STRESS AND ATHEROSCLEROSIS IN FEMALES

大豆、生命阶段、压力和女性动脉粥样硬化

• 批准号: 6993575
• 负责人: Jay Ross Kaplan
• 金额: $ 66.88万
• 依托单位: WAKE FOREST UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-01-01 至 2009-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6993575
• 关键词: Macaca fascicularis; age difference; atherosclerosis; behavioral /social science research tag; biopsy; coronary disorder; dietary constituent; dietary proteins; dietary supplements; estrogens; female; flavones; hormone regulation /control mechanism; menopause; nutrition of aging; nutrition related tag; ovariectomy; pathogenic diet; postmenopause; social status; soybeans; stress

DESCRIPTION (provided by applicant): The coronary heart disease (CHD) of postmenopausal women likely begins premenopausally and is exacerbated by estrogen deficiency. Thus, soy protein isolate with isoflavones (SOY), which is often consumed postmenopausally as a "heart healthy" supplement, may also offer premenopausal cardiovascular benefit. Yet, the optimal timing for intervention (in relation to menopausal status and lesion stage) remains uncertain, as does the extent of cardiovascular protection provided to women first exposed to SOY as adults. Premenopausal monkeys (Macaca fascicu/aris) are a surrogate for reproductive aged women in the study of atherosclerosis and CHD risk. In this model, the stress of social subordination (low status) induces estrogen deficiency, accelerates atherogenesis, and impairs vascular responsivity. Treatment of low status premenopausal females with exogenous estrogen reduces the extent of postmenopausal atherosclerosis independent of postmenopausal hormone exposure, demonstrating the potential benefit of premenopausal prevention. It is therefore proposed to expand the scope of an ongoing study that currently contains sociallyhoused, premenopausal monkeys consuming a moderately atherogenic diet, in which protein is derived from either SOY or casein-lactalbumin (C/L). This study was designed initially to determine whether SOY inhibits premenopausal coronary atherosclerosis in stressed individuals and whether such effects are influenced by endogenous estrogen. This design does not permit determination of the relative postmenopausal cardiovascular effects of pre- vs. postmenopausal SOY exposure, a comparison that could directly inform the treatment of postmenopausal women. The present application proposes to answer the odginai premenopausal study question by assessing atherosclerosis in an lilac artery biopsy (a validated coronary artery surrogate), eliminating the need to necropsy the premenopausal animals. Instead, the study will be extended to include a surgically postmenopausal phase which, by switching the protein source for half of the monkeys, will cross pre- and postmenopausal exposure to C/L and SOY in a 2 x 2 factorial design encompassing 4 treatment conditions (SOY ? SOY, SOY ? C/L, C/L ? SOY, and C/L ? C/L). The study will terminate with the evaluation of lilac, coronary, and carotid artery atherosclerosis. The aims are to test the hypothesis that the timing of SOY supplementation (pre- or postmenopausal) affects postmenopausal plaque progression and complications, and to determine the impact of chronic SOY exposure on noncardiovascutar, health-related outcomes.

描述（由申请人提供）：绝经后妇女的冠状动脉疾病（CHD）可能是开始前大规模开始的，并且因雌激素缺乏而加剧。因此，与异黄酮（大豆）分离的大豆蛋白通常在绝经后作为“心脏健康”补充剂食用，也可能提供绝经前心血管益处。然而，干预的最佳时机（与更年期状态和病变阶段有关）仍然不确定，向最初暴露于大豆成年的妇女提供的心血管保护程度也是如此。绝经前猴子（Macaca fascicu/aris）在研究动脉粥样硬化和CHD风险方面是生殖老年妇女的替代物。在此模型中，社会从属（低地位）的压力会诱导雌激素缺乏症，加速动脉粥样硬化并损害血管反应性。用外源性雌激素治疗低状态的绝经前女性可降低绝经后动脉粥样硬化的程度，而不是绝经后激素暴露，这表明预防前预防前预防前。因此，建议扩大一项正在进行的研究范围，该研究目前包含食用中等动脉粥样硬化饮食的社交前，绝经前猴子，其中蛋白质源自大豆或酪蛋白 - 乳糖蛋白（C/L）。这项研究最初旨在确定大豆是否抑制压力个体中的绝经前冠状动脉粥样硬化，以及这种作用是否受到内源性雌激素的影响。该设计不允许确定预赛与绝经后大豆暴露的绝经后心血管效应，这种比较可以直接为绝经后妇女的治疗提供信息。本应用建议通过评估丁香动脉活检（经过验证的冠状动脉替代物）中的动脉粥样硬化来回答Odginai的绝经前研究问题，从而消除了对末期前动物的必需品。取而代之的是，该研究将扩展到包括手术后的绝经后阶段，通过切换一半的猴子的蛋白质来源，将在2 x 2阶乘在c/l和大豆中跨越前后，在2 x 2阶乘设计中，涵盖4个治疗条件（soy？soy？这项研究将随着丁香，冠状动脉和颈动脉动脉粥样硬化的评估而终止。目的是检验以下假设：补充大豆的时机（绝经前或绝经后）会影响绝经后斑块的进展和并发症，并确定慢性大豆暴露对非脑抗性，与健康相关的结果的影响。