The Dichotomy of Estrogens in the Cardiovascular System

雌激素是一种迷人的激素，在心血管系统中有着看似矛盾的作用。一方面，雌激素似乎对绝经前妇女的心血管系统有保护作用。绝经前女性患心血管疾病的几率低于男性。绝经后发病率迅速增加，达到甚至超过男性。根据坊间证据和一些早期研究，人们普遍认为，雌激素的替代会使绝经后妇女的心血管系统恢复到绝经前的保护状态。然而，来自妇女健康倡议的早期数据并不支持这一假设；相反，这些数据表明，在用雌激素替代激素治疗的头两年，心血管事件有所增加。雌激素仍然是绝经前妇女最有可能的心血管保护因素。因此，我们提出，未能观察到雌激素对心血管功能的保护作用是由于给药的雌激素在心血管组织中是一种不完全的激动剂，或者以不适当的方式给药。本项目旨在验证雌激素对心血管系统的双重作用是由于不同雌激素配方和给药方式的不同基因表达反应。为了验证这一假设，已经提出了两个具体的目标。具体目标#1：研究血管组织中雌二醇17 β的基因表达谱，并研究雌激素制剂对肠系膜动脉血管反应性的影响。

Estrogen is a fascinating hormone with seemingly paradoxical effects in the cardiovascular system. On the one hand, estrogen appears to be protective to the cardiovascular system of pre-menopausal women. Prior to the menopause have a lower incidence of cardiovascular disease than men. After the menopause, the incidence increases rapidly to reach and even exceed that of men. It has been widely assumed, form anecdotal evidence, as ell as several early studies, that replacement of estrogen would return the cardiovascular system of the post-menopausal woman to its pre-menopausal protected state. However, the early data from the Women's Health Initiative does not support the assumption; rather, these data suggest an increase in cardiovascular events in the first two years of hormone replacement therapy with estrogen. Estrogen remains the most likely cardiovascular protective factor for pre-menopausal women. Thus we propose that the failure to observe a protective effect of estrogen on cardiovascular function is the result of administering an estrogen that is an incomplete agonist in cardiovascular tissues, or that is administered in inappropriate mode. This project is designed to test the hypothesis that the dichotomous effects of estrogen on the cardiovascular system are due to differential Gene expression responses to different estrogen formulations and modes of administration. Two specific aims have been developed to test this hypothesis. Specific aim #1: To develop a profile of genes expressed in response to estradiol 17beta in vascular tissues and to examine the effect of estrogen formulation on the vascular reactivity of the mesenteric arteries.