Mechanisms governing the protective effect of 17β-estradiol and estrogen receptors against cardiomyocyte injury

The sex hormone 17β-estradiol (E2) is the most abundant and active estrogen in premenopausal women. Studies have shown that high circulating levels of E2 are cardioprotective and are associated with reduced risk of developing heart disease in women of reproductive age. Estrogen receptors (ERs) are divided into three subtypes, namely ERα, ERβ, and GPR30, and these receptors have been shown to play important roles in E2-mediated pathways that protect cardiomyocytes from various cardiac insults, such as hypoxia, ischemic-reperfusion injury, sepsis, and hypertrophic agents. This review focuses on the role that estrogen and ER-mediated signaling pathways play in protecting cardiomyocytes against various stresses. Moreover, the therapeutic implication of selective ER-agonists on cardiomyopathy along with remaining unanswered issues are further discussed.