ESTROGEN STATUS AND THE FUNCTION OF CORONARY ARTERIES

雌激素可能对心血管疾病起到“保护作用” 绝经前妇女的疾病。此外， 绝经后妇女接受冠状动脉介入性手术 对男人来说比结果更糟糕。造成这种情况的原因尚不清楚。 这一提议的统一假设是性激素状态 影响激素受体(雌激素、孕激素和 雄激素)，进而调节结构和功能 冠状动脉的特点。这一提议的实验 代表了该领域内成熟的研究人员之间的合作 内分泌、血管内皮细胞和肌肉生理学。受体结合试验 将被用来量化受体的亲和力 女性冠状动脉中的雌激素、孕激素和雄激素 成年公猪、母猪和去卵巢母猪(特定目标1)。 动脉壁的结构特征将用 动脉壁基质蛋白的分子表征技术 以及性激素对它们的调节。这些蛋白质决定了 中将定义的动脉壁的粘弹性特性 分离的冠脉平滑肌条(特定目标2)。这个 性激素水平对大脑功能特征的影响 动脉将使用分子、细胞培养的组合进行评估。 和分离组织技术。这些功能特征包括 性激素水平与性激素受体表达的关系 细胞增殖，内皮源性一氧化氮的产生 和内皮素，血管内皮细胞上内皮素受体的数量和亲和力 平滑肌，以及性激素对敏感性(特异性)的影响 目标3)。所有结果将根据荷尔蒙状态进行评估 由循环性类固醇激素和数量定义的动物 雌激素受体。这些研究的结果将提供新的 关于性类固醇受体的调节以及它们如何 可能会影响冠状动脉的结构和功能。通过 了解这些基本的监管机制，可能会有选择性 可以开发预防和治疗冠状动脉疾病的治疗方法 人类的动脉疾病。

Estrogens may provide a "protective action" against cardiovascular disease for premenopausal women. Additionally, the outcome for postmenopausal women following interventional coronary artery procedures is worse than the outcome for men. The reasons for this are unclear. The unifying hypothesis of this proposal is that sex hormonal status affects expression of hormone receptors (estrogen, progesterone and androgen) which in turn regulates structural and functional characteristics of coronary arteries. The experiments of this proposal represent a collaboration among established investigators in the areas of endocrine, endothelia and muscle physiology. Receptor binding assays will be used to quantify the number of affinity of receptors for estrogen, progesterone and androgen in coronary arteries of sexually mature male, female and ovariectomized female pigs (Specific Aim 1). Structural characteristics of the arterial wall will be studied using molecular techniques to characterize matrix proteins in the arterial wall and their regulation by sex hormones. These proteins dictate the viscoelastic properties of the arterial wall which will be defined in isolated strips of coronary arterial smooth muscle (Specific Aim 2). The effects of sex hormonal status on the functional characteristics of the arteries will be evaluated using a combination of molecular, cell culture and isolated tissue techniques. These functional characteristics include the relationship of sex hormones and expression of hormone receptors on cell proliferation, the production of endothelium-derived nitric oxide and endothelins, the number and affinity of endothelin-receptors on the smooth muscle, and the effects of sex steroids on sensitivity (Specific Aim 3). All results will be assessed relative to the hormonal status of the animal as defined by circulating sex steroid hormones and the number of estrogen receptors. Results form these studies will provide new information about the regulation of sex steroid receptors and how they may affect the structure and function of coronary arteries. By understanding these basic regulatory mechanisms, potentially selective therapies can be developed for prevention and treatment of coronary artery disease in humans.