SOY, LIFE STAGE, STRESS AND ATHEROSCLEROSIS IN FEMALES

描述（由申请人提供）：绝经后妇女的冠心病（CHD）可能在绝经前开始，并因雌激素缺乏而加重。因此，大豆分离蛋白与大豆酮（SOY），这是经常消耗绝经后作为一个“心脏健康”的补充，也可能提供绝经前心血管的好处。然而，干预的最佳时机（与绝经状态和病变阶段有关）仍然不确定，对成年后首次暴露于SOY的女性提供的心血管保护程度也不确定。绝经前猴（Macaca fascicu/阿里斯）是研究动脉粥样硬化和CHD风险的育龄妇女的替代品。在这个模型中，社会从属关系（低地位）的压力诱导雌激素缺乏，加速动脉粥样硬化形成，并损害血管反应性。用外源性雌激素治疗低地位绝经前女性可降低绝经后动脉粥样硬化的程度，与绝经后激素暴露无关，表明绝经前预防的潜在益处。因此，建议扩大正在进行的研究的范围，该研究目前包含社会圈养的绝经前猴，这些猴食用中度致动脉粥样硬化饮食，其中蛋白质来源于SOY或酪蛋白-乳白蛋白（C/L）。这项研究最初的目的是确定大豆是否抑制绝经前冠状动脉粥样硬化的压力个人和这种影响是否受到内源性雌激素。该设计不允许确定绝经前与绝经后SOY暴露的相对绝经后心血管效应，这一比较可能直接为绝经后女性的治疗提供信息。本申请提出通过评估丁香动脉活组织检查（经验证的冠状动脉替代物）中的动脉粥样硬化来回答odginai绝经前研究问题，消除了对绝经前动物进行尸检的需要。相反，该研究将扩展到包括手术绝经后阶段，通过转换一半猴的蛋白质来源，将在2 x 2析因设计中交叉绝经前和绝经后暴露于C/L和SOY，包括4种治疗条件（SOY？SOY，SOY？信用证信用证SOY和C/L？C/L）。研究将在评价淡紫色、冠状动脉和颈动脉粥样硬化时结束。目的是检验补充SOY的时间（绝经前或绝经后）影响绝经后斑块进展和并发症的假设，并确定慢性SOY暴露对非心血管健康相关结局的影响。

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.