Coronary Reactivity and Thromboxane Receptor Expression

描述(来自应用程序的逐字)：冠状动脉反应性 调节是性腺的一种很少被认识但却很重要的结果 类固醇对灵长类动物血管的作用，因此这一因素具有深远的意义 更年期妇女衰老的意义。该项目旨在解决冠状动脉 高反应性是心脏病增加的一个方面，相对来说 被忽视了。女性患心脏病的风险随着年龄的增长而显著增加 更年期与雌激素(E)水平的下降密切相关， 和更深入的孕酮(P)，在持续存在的情况下 非卵巢E和睾酮(T)的产生。尤其是雄激素途径 双氢睾酮(DHT)似乎很重要。E&P&T的失衡， 这3种卵巢类固醇被认为会导致受保护状态的丧失。 此前，我们发现即使是亚生理水平的雌激素也会恢复 黄体酮恢复去卵巢大鼠正常冠脉反应性 灵长类动物。在这个项目中，手术治疗的更年期猴子将有2个 有E和/或P且DHT水平得到控制的周，或有2周增加的 或在控制E和P期间降低DHT，以进一步探讨冠状动脉 这3种类固醇激素的作用及其平衡。E、P和DHT似乎 生理调节冠脉反应性和血栓素A2 感受器。已知的最有效的TXA2受体诱导剂DHT形成 在冠状动脉局部，当存在不足时，大于1中的E 在没有P的情况下，平衡有利于将T转换为DHT而不是E.P 也直接抑制TXA2受体的表达。小于阈值P为 因此被认为是三重不利影响。E、P和TXA2的研究 免疫细胞化学方法研究TXA2受体在冠脉壁的分布 Scatchard分析受体结合、血E、P、DHT水平、冠脉 钙离子和蛋白激酶C的直径、血压和细胞研究 将对这些冠脉病变的病理生理机制进行探讨 对E、P和DHT进行多次操作的高反应性。活体内 导尿术实验室研究将与大体和 冠状动脉的组织病理学检查以确定相关性 高反应性和TXA2受体表达。E、P和DHT的测试 血管扩张剂和缩血管药变化对细胞因子的影响 在灵长类动物中冠状动脉对于理解如何保护 在绝经后衰老过程中预防冠状动脉风险。

DESCRIPTION (Verbatim from the application): Coronary artery reactivity modulation is a rarely recognized, but important, consequence of gonadal steroid actions on blood vessels of primates, and thus this factor has profound significance for aging in menopausal women. This project addresses coronary hyperreactivity as an aspect of increased heart disease that is relatively overlooked. The major increase in risk of heart disease with age in women during menopause is strongly correlated with falling levels of estrogens (E), and more profoundly of progesterone (P), in the presence of continued non-ovarian E and testosterone (T) production. The androgen path, particularly dihydrotestosterone (DHT), appears to be important. The imbalance of E & P & T, the 3 ovarian steroids, is hypothesized to lead to loss of a protected state. Previously, we showed that return of even subphysiological levels of estrogen and progesterone restores normal coronary reactivity in ovariectomized primates. In this project, surgically menopausal monkeys will be treated for 2 weeks with E and/or P with controlled levels of DHT, or with 2 week increases or decreases in DHT during controlled E and P, to further probe the coronary roles of these 3 steroid hormones and their balance. E, P, and DHT appear to physiologically regulate coronary reactivity and thromboxane A2 (TxA2) receptors. DHT, the most potent known inducer of TxA2 receptors is formed locally in coronary arteries, more than is E from 1, when there is a deficiency of P. Without P, the balance favors conversion of T to DHT rather than to E. P also directly suppresses TxA2 receptor expression. Less than threshold P is thus hypothesized to be a triple adverse influence. Studies of E, P, and TxA2 receptor distribution in the coronary artery wall by immunocytochemistry, TxA2 receptor binding by Scatchard analysis, blood levels of E, P, and DHT, coronary diameter, blood pressure, and cellular studies of Ca2+ and protein kinase C will be made to probe these pathophysiological mechanisms of coronary hyperreactivity with multiple manipulations of E, P, and DHT. In vivo catheterization laboratory studies will be combined with gross and histopathological examination of coronary arteries to determine correlations with hyperreactivity and TxA2 receptor expression. Tests of E, P, and DHT effects on cellular factors underlying vasodilator and vasoconstrictor changes in primate coronary arteries are important for understanding how to protect against coronary artery risks during the post-menopausal aging process.