Cardiovascular disease remains the leading cause of death for both men and women. The observation that premenopausal women are protected from cardiovascular disease relative to age-matched men, and that this protection is lost with menopause, has led to extensive study of the role of sex steroid hormones in the pathogenesis of cardiovascular disease. However, the molecular basis for sex differences in cardiovascular disease is still not fully understood, limiting the ability to tailor therapies to male and female patients. Therefore, there is a growing need to investigate molecular pathways outside of traditional sex hormone signaling to fully understand sex differences in cardiovascular disease. Emerging evidence points to the mineralocorticoid receptor (MR), a steroid hormone receptor activated by the adrenal hormone aldosterone, as one such mediator of cardiovascular disease risk, potentially serving as a sex-dependent link between cardiovascular risk factors and disease. Enhanced activation of the MR by aldosterone is associated with increased risk of cardiovascular disease. Emerging evidence implicates the MR specifically within the endothelial cells lining the blood vessels in mediating some of the sex differences observed in cardiovascular pathology. This review summarizes the available clinical and preclinical literature concerning the role of the MR in the pathophysiology of endothelial dysfunction, hypertension, atherosclerosis, and heart failure, with a special emphasis on sex differences in the role of endothelial-specific MR in these pathologies. The available data regarding the molecular mechanisms by which endothelial-specific MR may contribute to sex differences in cardiovascular disease is also summarized. A paradigm emerges from synthesis of the literature in which endothelial-specific MR regulates vascular function in a sex-dependent manner in response to cardiovascular risk factors to contribute to disease. Limitations in this field include the relative paucity of women in clinical trials and, until recently, the nearly exclusive use of male animals in preclinical investigations. Enhanced understanding of the sex-specific roles of endothelial MR could lead to novel mechanistic insights underlying sex differences in cardiovascular disease incidence and outcomes and could identify additional therapeutic targets to effectively treat cardiovascular disease in men and women.

中文翻译：

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内皮盐皮质激素受体：心血管疾病中性别差异的贡献。

心血管疾病仍然是男女死亡的主要原因。相对于年龄匹配的男性，绝经前的妇女受到心血管疾病的保护，而绝经后这种保护就消失了，这一发现导致人们对性类固醇激素在心血管疾病发病机理中的作用进行了广泛的研究。但是，心血管疾病中性别差异的分子基础仍然不完全清楚，这限制了针对男性和女性患者量身定制疗法的能力。因此，越来越需要研究传统性激素信号传导以外的分子途径，以充分了解心血管疾病中的性别差异。新兴证据表明，盐皮质激素受体（MR）是一种由肾上腺激素醛固酮激活的类固醇激素受体，作为心血管疾病风险的这种介导者之一，潜在地可作为心血管疾病危险因素与疾病之间的性别依赖性纽带。醛固酮增强的MR激活与心血管疾病的风险增加有关。越来越多的证据表明，MR介导了在心血管病理学中观察到的某些性别差异，特别是在血管内衬的内皮细胞内。这篇综述总结了有关MR在内皮功能障碍，高血压，动脉粥样硬化和心力衰竭的病理生理学中的作用的可用的临床和临床前文献，并特别强调了在这些病理学中内皮特异性MR的作用中的性别差异。还总结了有关内皮特异性MR可能有助于心血管疾病性别差异的分子机制的可用数据。文献综述中出现了一种范例，其中内皮特异性MR响应于心血管疾病的致病因素，以性别依赖性的方式调节血管功能。该领域的局限性包括在临床试验中女性相对缺乏，直到最近，在临床前研究中几乎只使用雄性动物。进一步了解内皮MR的性别特异性作用可能会导致新的机制洞察力，从而揭示心血管疾病发生率和预后方面的性别差异，并可能确定有效治疗男性和女性心血管疾病的其他治疗靶点。