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心血管和肾脏疾病中的 AT2 受体。

AT2 receptors in cardiovascular and renal diseases.

机构信息

Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Pharmacology, Center for Cardiovascular Research (CCR), Germany.

CARIM, Maastricht University, Maastricht, The Netherlands.

出版信息

Pharmacol Res. 2017 Nov;125(Pt A):39-47. doi: 10.1016/j.phrs.2017.07.008. Epub 2017 Jul 8.

Abstract

The renin-angiotensin system (RAS) plays an important role in the initiation and progression of cardiovascular and renal diseases. These actions mediated by AT1 receptor (AT1R) are well established and led to development of selective AT1R blockers (ARBs). In contrast, there is scientific evidence that AT2 receptor (AT2R) mediates effects different from and often opposing those of the AT1R. Meagrely expressed in healthy tissue the AT2R is upregulated in injuries providing an endogenous protection to inflammatory, oxidative and apoptotic processes. Interestingly the beneficial effects mediated by AT2R can be further enhanced by pharmacological intervention using the recently developed AT2R agonists. This review article summarizes our current knowledge about regulation, signalling and effects mediated by AT2R in health and disease, with emphasis on cardiac and renal systems. At the end a novel concept of natural protective systems will be introduced and discussed as an attractive target in drug development.

摘要

肾素-血管紧张素系统(RAS)在心血管和肾脏疾病的发生和进展中起着重要作用。这些由 AT1 受体(AT1R)介导的作用已得到充分证实,并导致了选择性 AT1R 阻滞剂(ARB)的开发。相比之下,有科学证据表明 AT2 受体(AT2R)介导的作用与 AT1R 不同,并且通常与 AT1R 相反。AT2R 在健康组织中表达很少,但在损伤时上调,为炎症、氧化和细胞凋亡过程提供内源性保护。有趣的是,使用最近开发的 AT2R 激动剂进行药理学干预可以进一步增强 AT2R 介导的有益作用。本文综述了我们目前对 AT2R 在健康和疾病中的调节、信号转导和作用的认识,重点介绍了心脏和肾脏系统。最后,将介绍和讨论一种新的天然保护系统概念,作为药物开发的一个有吸引力的靶点。

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