Chakrabarti Subhadeep, Morton Jude S, Davidge Sandra T
Department of Obstetrics and Gynecology, Women and Children's Health Research Institute (WCHRI), Cardiovascular Research Centre and Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
Department of Obstetrics and Gynecology, Women and Children's Health Research Institute (WCHRI), Cardiovascular Research Centre and Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada; Department of Physiology, Women and Children's Health Research Institute (WCHRI), Cardiovascular Research Centre and Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
Can J Cardiol. 2014 Jul;30(7):705-12. doi: 10.1016/j.cjca.2013.08.006. Epub 2013 Nov 16.
In this review, we aim to provide an overview of the recent advances in understanding estrogen effects on the vascular endothelium. Epidemiological studies suggest the female sex hormone estrogen mediates the relative protection of premenopausal women against cardiovascular disease, compared with age-matched men. However, results from clinical trials of exogenous estrogen supplementation in postmenopausal women have been disappointing, generating much controversy about the role of estrogen and demonstrating the need for further research in this field. Here we have discussed the roles of different estrogen receptors (ERs) such as ERα, ERβ, and G-protein coupled receptor 30; the complex genomic and nongenomic signalling pathways downstream to ER activation and the factors such as age, menopause, pregnancy, and diabetes that might alter estrogen responses. The common themes of this discussion are the complexity and diversity of endothelial estrogen responses and their modulation by 1 or more coexisting factors. Finally, we summarize the emerging therapeutic options including improved targeting of individual ERs and signalling pathways that might maximize the therapeutic potential of estrogenic compounds while minimizing their harmful side effects.
在本综述中，我们旨在概述近期在理解雌激素对血管内皮作用方面取得的进展。流行病学研究表明，与年龄匹配的男性相比，女性性激素雌激素介导了绝经前女性对心血管疾病的相对保护作用。然而，绝经后女性补充外源性雌激素的临床试验结果却令人失望，引发了关于雌激素作用的诸多争议，并表明该领域需要进一步研究。在此，我们讨论了不同雌激素受体（ERs）的作用，如ERα、ERβ和G蛋白偶联受体30；ER激活下游复杂的基因组和非基因组信号通路，以及可能改变雌激素反应的因素，如年龄、绝经、妊娠和糖尿病。本次讨论的共同主题是内皮雌激素反应的复杂性和多样性，以及它们受一种或多种共存因素的调节。最后，我们总结了新出现的治疗选择，包括改进对个体ERs和信号通路的靶向作用，这可能在将雌激素化合物的有害副作用降至最低的同时，最大限度地发挥其治疗潜力。
