The protective role of estrogen and estrogen receptors in cardiovascular disease and the controversial use of estrogen therapy.
The protective role of estrogen and estrogen receptors in cardiovascular disease and the controversial use of estrogen therapy.
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DOI：
10.1186/s13293-017-0152-8
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发表时间：
2017-10-24
影响因子：
7.9
通讯作者：
Eghbali M
中科院分区：
文献类型：
--
作者：
Iorga A;Cunningham CM;Moazeni S;Ruffenach G;Umar S;Eghbali M
流行病学研究表明，与年龄匹配的男性相比，绝经前女性心血管疾病（CVD）的发病率降低，绝经后CVD的发病率和严重程度增加。育龄妇女心血管疾病的发病率较低，至少部分归因于雌激素（E2）。E2与传统的E2受体（ER）、雌激素受体α（ERα）和雌激素受体β（ERβ）以及最近鉴定的G蛋白偶联ER（GPR30）结合，并可发挥基因组和非基因组作用。本文综述了E2及其受体在心血管系统中的保护作用，并讨论了其潜在的机制，重点是氧化应激，纤维化，血管生成和血管功能。这篇综述还介绍了雌激素受体在心血管疾病中调节E2作用的性二态性作用。由于血栓形成事件、癌症和心律失常的可能风险，围绕外源性E2作为女性心血管疾病治疗剂的临床使用的争议也进行了讨论。睾酮通过芳香酶转化为E2的内源性局部E2生物合成提供了一种新的治疗范式。靶向心血管系统中的特异性ER可能会产生新的和可能更安全的心血管保护治疗选择。
Epidemiologic studies have previously suggested that premenopausal females have reduced incidence of cardiovascular disease (CVD) when compared to age-matched males, and the incidence and severity of CVD increases postmenopause. The lower incidence of cardiovascular disease in women during reproductive age is attributed at least in part to estrogen (E2). E2 binds to the traditional E2 receptors (ERs), estrogen receptor alpha (ERα), and estrogen receptor beta (ERβ), as well as the more recently identified G-protein-coupled ER (GPR30), and can exert both genomic and non-genomic actions. This review summarizes the protective role of E2 and its receptors in the cardiovascular system and discusses its underlying mechanisms with an emphasis on oxidative stress, fibrosis, angiogenesis, and vascular function. This review also presents the sexual dimorphic role of ERs in modulating E2 action in cardiovascular disease. The controversies surrounding the clinical use of exogenous E2 as a therapeutic agent for cardiovascular disease in women due to the possible risks of thrombotic events, cancers, and arrhythmia are also discussed. Endogenous local E2 biosynthesis from the conversion of testosterone to E2 via aromatase enzyme offers a novel therapeutic paradigm. Targeting specific ERs in the cardiovascular system may result in novel and possibly safer therapeutic options for cardiovascular protection.