Department of Medicine-Endocrinology and Metabolism, University of Missouri School of Medicine, Columbia, Missouri, USA.
Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri, USA.
J Mol Endocrinol. 2023 Sep 13;71(3). doi: 10.1530/JME-23-0066. Print 2023 Oct 1.
Metabolic syndrome is a group of risk factors that increase the risk of developing metabolic and cardiovascular disease (CVD) and include obesity, dyslipidemia, insulin resistance, atherosclerosis, hypertension, coronary artery disease, and heart failure. Recent research indicates that excessive production of aldosterone and associated activation of mineralocorticoid receptors (MR) impair insulin metabolic signaling, promote insulin resistance, and increase the risk of developing metabolic syndrome and CVD. Moreover, activation of specific epithelial sodium channels (ENaC) in endothelial cells (EnNaC), which are downstream targets of endothelial-specific MR (ECMR) signaling, are also believed to play a crucial role in the development of metabolic syndrome and CVD. These adverse effects of ECMR/EnNaC activation are mediated by increased oxidative stress, inflammation, and lipid metabolic disorders. It is worth noting that ECMR/EnNaC activation and the pathophysiology underlying metabolic syndrome and CVD appears to exhibit sexual dimorphism. Targeting ECMR/EnNaC signaling may have a beneficial effect in preventing insulin resistance, diabetes, metabolic syndrome, and related CVD. This review aims to examine our current understanding of the relationship between MR activation and increased metabolic syndrome and CVD, with particular emphasis placed on the role for endothelial-specific ECMR/EnNaC signaling in these pathological processes.
代谢综合征是一组增加代谢和心血管疾病（CVD）风险的危险因素，包括肥胖、血脂异常、胰岛素抵抗、动脉粥样硬化、高血压、冠心病和心力衰竭。最近的研究表明，醛固酮的过度产生和相关的盐皮质激素受体（MR）激活会损害胰岛素代谢信号，促进胰岛素抵抗，并增加代谢综合征和 CVD 的发病风险。此外，内皮细胞中特定上皮钠离子通道（ENaC）的激活（ENaC），是内皮特异性 MR（ECMR）信号的下游靶点，也被认为在代谢综合征和 CVD 的发展中起着至关重要的作用。这些 ECMR/EnNaC 激活的不良影响是通过增加氧化应激、炎症和脂质代谢紊乱来介导的。值得注意的是，ECMR/EnNaC 激活和代谢综合征及 CVD 的病理生理学似乎表现出性别二态性。靶向 ECMR/EnNaC 信号可能对预防胰岛素抵抗、糖尿病、代谢综合征和相关 CVD 有益。本综述旨在探讨我们目前对 MR 激活与代谢综合征和 CVD 增加之间关系的理解，特别强调内皮特异性 ECMR/EnNaC 信号在这些病理过程中的作用。
