ER beta selective agonist coronary protection--menopause

描述(申请人提供)：这个第一阶段项目的目标是在体外利用灵长类冠状动脉血管肌肉细胞测试和开发一种新的雌激素受体β(ERbeta)选择性(超过ERpha)激动剂，该激动剂对保护冠状动脉免受过度反应和缓解心血管更年期卵巢类固醇缺乏症状非常有效。这种心血管高反应性似乎是由于卵巢功能停止后缺乏平衡的雌激素ERβ和ERα受体刺激所致。这个项目将检验ERbeta激动剂(ERbetaA)的作用，ERbetaA是一种天然的人类类固醇代谢物，在恒河猴冠状动脉血管肌肉细胞实验中作为基因组反应性抑制因子的新适应症。该项目旨在解决减少更年期妇女冠状动脉功能障碍、残疾和死亡率的挑战。心血管疾病是50岁以上女性和男性的主要死亡风险，与类固醇产生减少和类固醇受体平衡有关的机制尚不清楚。拟议的ERbetaA提法旨在显著改善这一状况，提高男女的生活质量。新的商业产品将是一种旨在通过提供第一种提供ERbeta选择性刺激的试剂来促进目前状态的配方。ERbetaA简介是有益的，因为它包括预防冠状动脉高反应性，同时降低乳腺癌和子宫癌的风险。此外，只需要低浓度的这种生物相同的代谢物预示着极好的安全性和副作用前景。选择性刺激ERbeta似乎是理想的，因为它对冠状动脉高反应性以及乳腺癌和子宫癌具有多方面的保护作用。

DESCRIPTION (provided by applicant): The objective of this Phase I project is to test and develop, using primate coronary artery vascular muscle cells in vitro, a novel estrogen receptor beta (ERbeta) selective (over ERalpha) agonist that is highly effective for protecting coronary arteries against hyperreactivity and also for relieving cardiovascular menopausal symptoms of ovarian steroid deficiency. Such cardiovascular hyperreactivity appears to result from the deficiency of balanced estrogen ERbeta versus ERalpha receptor stimulation after the cessation of ovarian function. This project will examine the effect of the ERbeta Agonist (ERbetaA), which is a natural human steroid metabolite, for the novel indication as a genomic repressor of reactivity in rhesus coronary vascular muscle cell experiments. This project is addressed to the challenge of reduction of coronary dysfunction, disability, and fatalities in menopausal women. Cardiovascular disease, the leading risk of death for women and men over age 50, mechanisms related to declining steroid production and steroid receptor balance are not well understood. The proposed ERbetaA formulation has been designed to significantly improve this situation and enhance quality of life in both women and men. The new commercial product will be a formulation designed to advance the present state by providing the first agent to offer ERbeta selective stimulation. The ERbetaA profile is salutary as it includes protection against coronary hyperreactivity while simultaneously lowering the risk of breast and uterine cancer. Furthermore, the need for only a low concentration of this bioidentical metabolite portends an excellent safety and side-effect prospect. Selective stimulation of ERbeta appears ideal because of this multifaceted protection against coronary hyperreactivity and of breast and uterine carcinomas.