Programa de Pesquisa em Desenvolvimento de Fármacos, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.
Instituto de Cardiologia Edson Saad, Faculdade de Medicina, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941-902, Brazil.
Int J Mol Sci. 2021 Jan 7;22(2):525. doi: 10.3390/ijms22020525.
Estrogen receptors (ER) mediate functions beyond their endocrine roles, as modulation of cardiovascular, renal, and immune systems through anti-inflammatory and anti-apoptotic effects, preventing necrosis of cardiomyocytes and endothelial cells, and attenuating cardiac hypertrophy. Estradiol (E2) prevents cardiac dysfunction, increases nitric oxide synthesis, and reduces the proliferation of vascular cells, yielding protective effects, regardless of gender. Such actions are mediated by ER (ER-alpha (ERα), ER-beta (ERβ), or G protein-coupled ER (GPER)) through genomic or non-genomic pathways, which regulate cardiovascular function and prevent tissue remodeling. Despite the extensive knowledge on the cardioprotective effects of estrogen, clinical studies conducted on myocardial infarction (MI) and cardiovascular diseases still include favorable and unfavorable profiles. The purpose of this review is to provide up-to-date information regarding molecular, preclinical, and clinical aspects of cardiovascular E2 effects and ER modulation as a potential therapeutic target for the treatment of MI-induced cardiac dysfunction.
雌激素受体 (ER) 通过抗炎和抗凋亡作用介导心血管、肾脏和免疫系统的功能，防止心肌细胞和内皮细胞坏死，并减轻心脏肥大，超出其内分泌作用。雌二醇 (E2) 可预防心脏功能障碍、增加一氧化氮合成并减少血管细胞增殖，产生保护作用，而与性别无关。这些作用通过 ER（ER-α (ERα)、ER-β (ERβ) 或 G 蛋白偶联 ER (GPER)) 通过基因组或非基因组途径介导，调节心血管功能并预防组织重塑。尽管对雌激素的心脏保护作用有广泛的了解，但在心肌梗死 (MI) 和心血管疾病方面进行的临床研究仍包括有利和不利的结果。本综述的目的是提供有关心血管 E2 作用和 ER 调节的分子、临床前和临床方面的最新信息，作为治疗 MI 诱导的心脏功能障碍的潜在治疗靶点。
