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醛固酮和盐皮质激素受体在心血管疾病中的新作用:转化和性别特异性效应。

New roles of aldosterone and mineralocorticoid receptors in cardiovascular disease: translational and sex-specific effects.

机构信息

Department of Structural and Functional Biology, Institute of Biology, University of Campinas , Campinas, Sâo Paulo , Brazil.

Molecular Cardiology Research Institute Tufts Medical Center , Boston, Massachusetts.

出版信息

Am J Physiol Heart Circ Physiol. 2018 Oct 1;315(4):H989-H999. doi: 10.1152/ajpheart.00073.2018. Epub 2018 Jun 29.

Abstract

Recent advances in the field of mineralocorticoid receptor (MR) and its ligand aldosterone expanded the role of this hormone and its receptor far beyond their initial function as a regulator of Na and K homeostasis in epithelial cells. The symposium "New Roles of Aldosterone and Mineralocorticoid Receptors in Cardiovascular Disease: Translational and Sex-Specific Effects" presented at the 38th World Congress of the International Union of Physiological Sciences (Rio de Janeiro, Brazil) highlighted the contribution of extrarenal MRs to cardiovascular disease. This symposium showcased how MRs expressed in endothelial, vascular smooth muscle, and immune cells plays a critical role in the development of vascular disease associated with aging, obesity, and chronic aldosterone stimulation and demonstrated that MR antagonism prevents the acute renal dysfunction and tubular injury induced by ischemia-reperfusion injury. It was also shown that the adipocyte-derived hormone leptin is a new direct regulator of aldosterone secretion and that leptin-mediated aldosterone production is a major contributor to obesity-associated hypertension in women. Sex differences in the role of aldosterone and of endothelial MR in the cardiovascular outcomes of obesity were highlighted. This review summarizes these important emerging concepts regarding the contribution of aldosterone and cell-specific MR to cardiovascular disease in male and female subjects and further supports sex-specific benefits of MR antagonist drugs to be tested in additional populations.

摘要

近年来,醛固酮受体(MR)及其配体醛固酮领域的研究进展极大地扩展了这种激素及其受体的作用,远远超出了它们最初作为上皮细胞中钠和钾稳态调节剂的功能。在第 38 届国际生理科学联合会世界大会(巴西里约热内卢)上举办的“醛固酮和盐皮质激素受体在心血管疾病中的新作用:转化和性别特异性影响”专题研讨会强调了肾脏外 MR 对心血管疾病的贡献。该研讨会展示了内皮细胞、血管平滑肌和免疫细胞中表达的 MR 如何在与衰老、肥胖和慢性醛固酮刺激相关的血管疾病的发展中发挥关键作用,并表明 MR 拮抗剂可预防缺血再灌注损伤引起的急性肾功能障碍和肾小管损伤。研究还表明,脂肪细胞衍生的激素瘦素是醛固酮分泌的新的直接调节剂,瘦素介导的醛固酮产生是女性肥胖相关性高血压的主要原因。强调了醛固酮和内皮 MR 在肥胖对心血管结局的作用中的性别差异。这篇综述总结了这些关于醛固酮和细胞特异性 MR 对男性和女性心血管疾病的贡献的重要新观点,并进一步支持在其他人群中测试 MR 拮抗剂药物的性别特异性获益。

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