The Dichotomy of Estrogens in the Cardiovascular System

雌激素在心血管系统中的二分法

• 批准号: 6457353
• 负责人: KATHLEEN M EYSTER
• 金额: $ 14.05万
• 依托单位: UNIVERSITY OF SOUTH DAKOTA
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-02-15 至 2005-02-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6457353
• 关键词: cardiovascular disorder risk; chemoprevention; cytoprotection; dosage forms; drug administration routes; estrogens; female; gene expression; in situ hybridization; laboratory rat; microarray technology; northern blottings; ovariectomy; vasomotion

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.

雌激素是一种迷人的激素，在心血管系统中具有看似矛盾的作用。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。绝经前有较低的心血管疾病的发病率比男性。绝经后，发病率迅速上升，达到甚至超过男性。从轶事证据以及一些早期研究中，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，在使用雌激素替代疗法的前两年，心血管事件增加。雌激素仍然是绝经前妇女最可能的心血管保护因素。因此，我们认为，未能观察到雌激素对心血管功能的保护作用是由于给予雌激素在心血管组织中是不完全激动剂，或以不适当的方式给予。该项目旨在验证雌激素对心血管系统的二分效应是由于不同雌激素制剂和给药方式的差异基因表达反应的假设。为了检验这一假设，已经制定了两个具体目标。具体目标1：建立血管组织中对雌二醇17 β反应的基因表达谱，并检测雌激素制剂对肠系膜动脉血管反应性的影响。