SOY, LIFE STAGE, STRESS AND ATHEROSCLEROSIS IN FEMALES

描述(申请人提供)：绝经后妇女的冠心病(CHD)很可能在绝经前就开始，并因雌激素缺乏而加重。因此，大豆分离蛋白和异黄酮类(大豆)，通常在绝经后食用作为“心脏健康”的补充，也可能提供绝经前的心血管益处。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，对成年后首次接触大豆的妇女提供的心血管保护程度也不确定。在动脉粥样硬化和冠心病风险的研究中，绝经前的猕猴是育龄妇女的替代品。在这个模型中，社会从属(低地位)的压力导致雌激素缺乏，加速动脉粥样硬化形成，并削弱血管反应性。用外源性雌激素治疗绝经前状态较低的女性可以减少绝经后动脉粥样硬化的程度，而不依赖于绝经后激素的暴露，这表明了绝经前预防的潜在好处。因此，提议扩大目前正在进行的一项研究的范围，该研究目前包括社会饲养的绝经前猴子，它们食用中度致动脉粥样硬化的饮食，其中蛋白质来自大豆或酪蛋白-乳清蛋白(C/L)。这项研究最初是为了确定大豆是否能抑制应激个体的绝经前冠状动脉粥样硬化，以及这种作用是否受内源性雌激素的影响。这项设计不允许确定绝经前和绝经后大豆暴露对绝经后心血管的相对影响，这种比较可以直接为绝经后妇女的治疗提供参考。本申请建议通过评估丁香动脉活检(一种有效的冠状动脉替代物)中的动脉粥样硬化来回答odgiai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，这项研究将扩展到包括手术绝经后阶段，通过改变一半猴子的蛋白质来源，将在绝经前和绝经后暴露于C/L和大豆，采用2 x 2析因设计，包括4种治疗条件(大豆？大豆，大豆？L，L？大豆，和C/L？C/L)。这项研究将以丁香动脉、冠状动脉和颈动脉粥样硬化的评估结束。其目的是验证大豆补充时机(绝经前或绝经后)影响绝经后斑块进展和并发症的假设，并确定长期接触大豆对非心血管疾病和健康相关结果的影响。

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.