Division of Clinical Epigenetics, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
Shinshu University School of Medicine, Nagano, Japan.
J Am Soc Nephrol. 2021 Feb;32(2):279-289. doi: 10.1681/ASN.2020071041. Epub 2021 Jan 4.
Hypertension and its comorbidities pose a major public health problem associated with disease-associated factors related to a modern lifestyle, such high salt intake or obesity. Accumulating evidence has demonstrated that aldosterone and its receptor, the mineralocorticoid receptor (MR), have crucial roles in the development of salt-sensitive hypertension and coexisting cardiovascular and renal injuries. Accordingly, clinical trials have repetitively shown the promising effects of MR blockers in these diseases. We and other researchers have identified novel mechanisms of MR activation involved in salt-sensitive hypertension and renal injury, including the obesity-derived overproduction of aldosterone and ligand-independent signaling. Moreover, recent advances in the analysis of cell-specific and context-dependent mechanisms of MR activation in various tissues-including a classic target of aldosterone, aldosterone-sensitive distal nephrons-are now providing new insights. In this review, we summarize recent updates to our understanding of aldosterone-MR signaling, focusing on its role in salt-sensitive hypertension and renal injury.
高血压及其合并症是一个主要的公共卫生问题,与现代生活方式相关的疾病相关因素有关,如高盐摄入或肥胖。越来越多的证据表明,醛固酮及其受体,即盐皮质激素受体(MR),在盐敏感性高血压和并存的心血管和肾脏损伤的发展中起着关键作用。因此,临床试验反复表明,MR 阻滞剂在这些疾病中的治疗效果很有前景。我们和其他研究人员已经确定了参与盐敏感性高血压和肾损伤的新型 MR 激活机制,包括肥胖引起的醛固酮过度产生和非配体依赖性信号传导。此外,最近在分析各种组织中 MR 激活的细胞特异性和上下文依赖性机制方面的进展,包括醛固酮的经典靶标醛固酮敏感的远曲小管,提供了新的见解。在这篇综述中,我们总结了我们对醛固酮-MR 信号转导的最新认识,重点讨论了其在盐敏感性高血压和肾损伤中的作用。