Department of Physiology and Biophysics, National Institute of Science and Technology in Nanobiopharmaceutics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte (MG), Brazil.
Clin Sci (Lond). 2013 Apr;124(7):443-56. doi: 10.1042/CS20120461.
It is well known that the RAS (renin-angiotensin system) plays a key role in the modulation of many functions in the body. AngII (angiotensin II) acting on AT1R (type 1 AngII receptor) has a central role in mediating most of the actions of the RAS. However, over the past 10 years, several studies have presented evidence for the existence of a new arm of the RAS, namely the ACE (angiotensin-converting enzyme) 2/Ang-(1-7) [angiotensin-(1-7)]/Mas axis. Ang-(1-7) can be produced from AngI or AngII via endo- or carboxy-peptidases respectively. ACE2 appears to play a central role in Ang-(1-7) formation. As described for AngII, Ang-(1-7) also has a broad range of effects in different organs and tissues which goes beyond its initially described cardiovascular and renal actions. Those effects are mediated by Mas and can counter-regulate most of the deleterious effects of AngII. The interaction Ang-(1-7)/Mas regulates different signalling pathways, such as PI3K (phosphoinositide 3-kinase)/AKT and ERK (extracellularsignal-regulated kinase) pathways and involves downstream effectors such as NO, FOXO1 (forkhead box O1) and COX-2 (cyclo-oxygenase-2). Through these mechanisms, Ang-(1-7) is able to improve pathological conditions including fibrosis and inflammation in organs such as lungs, liver and kidney. In addition, this heptapeptide has positive effects on metabolism, increasing the glucose uptake and lipolysis while decreasing insulin resistance and dyslipidaemia. Ang-(1-7) is also able to improve cerebroprotection against ischaemic stroke, besides its effects on learning and memory. The reproductive system can also be affected by Ang-(1-7) treatment, with enhanced ovulation, spermatogenesis and sexual steroids synthesis. Finally, Ang-(1-7) is considered a potential anti-cancer treatment since it is able to inhibit cell proliferation and angiogenesis. Thus the ACE2/Ang-(1-7)/Mas pathway seems to be involved in many physiological and pathophysiological processes in several systems and organs especially by opposing the detrimental effects of inappropriate overactivation of the ACE/AngII/AT1R axis.
众所周知，RAS（肾素-血管紧张素系统）在调节体内许多功能方面起着关键作用。AngII（血管紧张素 II）作用于 AT1R（血管紧张素 II 型 1 型受体），在介导 RAS 的大多数作用中起着核心作用。然而，在过去的 10 年中，有几项研究已经证明了 RAS 的一个新分支的存在，即 ACE（血管紧张素转换酶）2/Ang-（1-7）[血管紧张素-（1-7）]/Mas 轴。Ang-（1-7）可以分别通过内肽酶或羧肽酶从 AngI 或 AngII 中产生。ACE2 似乎在 Ang-（1-7）形成中起核心作用。与 AngII 一样，Ang-（1-7）在不同的器官和组织中也具有广泛的作用，超出了其最初描述的心血管和肾脏作用。这些作用是由 Mas 介导的，可以对抗 AngII 的大多数有害作用。Ang-（1-7）/Mas 的相互作用调节不同的信号通路，如 PI3K（磷酸肌醇 3-激酶）/AKT 和 ERK（细胞外信号调节激酶）通路，并涉及下游效应物，如 NO、FOXO1（叉头框 O1）和 COX-2（环氧化酶-2）。通过这些机制，Ang-（1-7）能够改善包括肺、肝和肾等器官的纤维化和炎症等病理状况。此外，这种七肽对代谢有积极影响，增加葡萄糖摄取和脂肪分解，同时降低胰岛素抵抗和血脂异常。Ang-（1-7）还能够改善缺血性中风的脑保护作用，以及对学习和记忆的作用。生殖系统也可以受到 Ang-（1-7）治疗的影响，增强排卵、精子发生和性类固醇合成。最后，Ang-（1-7）被认为是一种潜在的抗癌治疗方法，因为它能够抑制细胞增殖和血管生成。因此，ACE2/Ang-（1-7）/Mas 途径似乎参与了多个系统和器官的许多生理和病理生理过程，特别是通过对抗 ACE/AngII/AT1R 轴过度激活的不利影响。
