Dworatzek Elke, Mahmoodzadeh Shokoufeh
Institut of Gender in Medicine and Center for Cardiovascular Research, Charitè-Universitaetsmedizin Berlin, Berlin, Germany; DZHK (German Center for Cardiovascular Research, partner site Berlin), Berlin, Germany.
Max-Delbrueck-Center for Molecular Medicine, Berlin, Germany; DZHK (German Center for Cardiovascular Research, partner site Berlin), Berlin, Germany.
Pharmacol Res. 2017 May;119:27-35. doi: 10.1016/j.phrs.2017.01.019. Epub 2017 Jan 21.
Epidemiological, clinical and animal studies revealed that sex differences exist in the manifestation and outcome of cardiovascular disease (CVD). The underlying molecular mechanisms implicated in these sex differences are not fully understood. The reasons for sex differences in CVD are definitely multifactorial, but major evidence points to the contribution of sex steroid hormone, 17β-estradiol (E2), and its receptors, estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ). In this review, we summarize past and present studies that implicate E2 and ER as important determinants of sexual dimorphism in the physiology and pathophysiology of the heart. In particular, we give an overview of studies aimed to reveal the role of E2 and ER in the physiology of the observed sex differences in CVD using ER knock-out mice. Finally, we discuss recent findings from novel transgenic mouse models, which have provided new information on the sexual dimorphic roles of ER specifically in cardiomyocytes under pathological conditions.
流行病学、临床及动物研究表明，心血管疾病（CVD）的表现及转归存在性别差异。这些性别差异背后的分子机制尚未完全明确。CVD性别差异的原因肯定是多因素的，但主要证据表明性甾体激素17β-雌二醇（E2）及其受体雌激素受体α（ERα）和雌激素受体β（ERβ）发挥了作用。在本综述中，我们总结了过去和现在的研究，这些研究表明E2和ER是心脏生理和病理生理中性二态性的重要决定因素。特别是，我们概述了旨在利用ER基因敲除小鼠揭示E2和ER在CVD中观察到的性别差异生理过程中作用的研究。最后，我们讨论了新型转基因小鼠模型的最新研究结果，这些研究为ER在病理条件下心肌细胞中的性别二态性作用提供了新信息。
