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醛固酮在心血管系统中的新作用:治疗干预的潜在靶点。

New Sides of Aldosterone Action in Cardiovascular System as Potential Targets for Therapeutic Intervention.

机构信息

Department of Experimental and Clinical Pharmacology, Faculty of Medicine, University of Rzeszow, Poland.

Department of Biopharmacy, Faculty of Pharmacy with the Division of Laboratory Medicine, Medical University of Bialystok, Poland.

出版信息

Curr Drug Targets. 2018;19(16):1968-1979. doi: 10.2174/1389450119666180326125926.

Abstract

Aldosterone, the main mineralocorticoid hormone, plays a crucial role in the regulation of electrolyte homeostasis and blood pressure. Although this role is undoubtedly important, it is not a hormonal action that attracts the most attention. Aldosterone seems to be very important as a local messenger in the pathology of cardiovascular diseases (CVD). In the last few years, the attention was focused on the correlation between raised aldosterone level and increased risk of cardiovascular events. It has been demonstrated that aldosterone contributes to fibrosis, inflammation, endothelial dysfunction, fibrinolytic disorders, and oxidative stress leading to CVD development and progression. It used to be thought that the effects of aldosterone are mediated via classic nuclear receptors - mineralocorticoid receptors (MRs). Now we know that the mechanism of aldosterone action in the cardiovascular system (CVS) is much more complex since experimental and clinical studies indicate that MR blockade may be not sufficient to abolish aldosterone-induced harmful effects in CVS. Thus, the involvement of some other than MR, receptors, and factors is suggested. Moreover, in addition to the generally known genomic action of aldosterone, which involves MR activation, the nongenomic pathways are postulated in the mode of hormone action. More and more attention is focused on the membrane-coupled receptors, which mediate the rapid effects of aldosterone and have been already confirmed in different cells and tissues of CVS. Therefore, this brief review summarizes recent findings about new sides of aldosterone action in CVS that could be potential targets for therapeutic intervention.

摘要

醛固酮是主要的盐皮质激素,在电解质稳态和血压调节中起着关键作用。虽然这种作用无疑很重要,但它并不是最受关注的激素作用。醛固酮在心血管疾病 (CVD) 的病理生理学中作为局部信使似乎非常重要。在过去的几年中,人们关注的焦点是醛固酮水平升高与心血管事件风险增加之间的相关性。已经证明醛固酮有助于纤维化、炎症、内皮功能障碍、纤维蛋白溶解紊乱和氧化应激,从而导致 CVD 的发生和进展。过去认为醛固酮的作用是通过经典的核受体-盐皮质激素受体 (MRs) 介导的。现在我们知道,醛固酮在心血管系统 (CVS) 中的作用机制要复杂得多,因为实验和临床研究表明,MR 阻断可能不足以消除醛固酮在 CVS 中引起的有害影响。因此,除了通常认为的醛固酮通过 MR 激活的基因组作用外,还提出了一些其他受体和因素的参与。此外,除了涉及 MR 激活的醛固酮的一般已知的基因组作用外,还提出了激素作用的非基因组途径。越来越多的人关注膜偶联受体,它们介导醛固酮的快速作用,并已在 CVS 的不同细胞和组织中得到证实。因此,这篇简要综述总结了醛固酮在 CVS 中作用的新方面的最新发现,这些新方面可能是治疗干预的潜在靶点。

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