Devil and angel in the renin-angiotensin system: ACE-angiotensin II-AT1 receptor axis vs. ACE2-angiotensin-(1-7)-Mas receptor axis.
Devil and angel in the renin-angiotensin system: ACE-angiotensin II-AT1 receptor axis vs. ACE2-angiotensin-(1-7)-Mas receptor axis.
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肾素 - 血管紧张素系统中的魔鬼和天使：ACE-血管紧张素II-AT1受体轴与ACE2-血管紧张素 - （1-7） - Mas受体轴。
DOI：
10.1038/hr.2009.74
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发表时间：
2009-07
期刊：
影响因子：
--
通讯作者：
Horiuchi M
中科院分区：
文献类型：
--
作者：
Iwai M;Horiuchi M
最近的研究在肾素-血管紧张素系统（RAS）中建立了一个新的调节轴。在此轴上，血管紧张素（Ang）-（1-7）最终由血管紧张素I或血管紧张素II在血管紧张素转换酶2（ACE2）的催化活性下产生。 Ang-(1-7) 显示出与 AT1 受体刺激不同的作用，例如血管舒张、排尿钠、抗增殖和缓激肽-NO（一氧化氮）系统的增加。由于以 Ang II 作为底物时 ACE2 的催化效率比以 Ang I 为底物高约 400 倍，因此该轴可能充当针对 ACE/Ang II/AT1 受体轴的反调节系统。 ACE2–Ang-(1–7) 轴的信号通路尚未完全清楚地了解。然而，最近的一份报告表明 Mas 癌基因充当 Ang-(1-7) 的受体。通过 Mas 的细胞内信号传导尚不清楚。 Akt 磷酸化、蛋白激酶 C 激活和丝裂原激活蛋白 (MAP) 激酶抑制等多种因素似乎与该信号通路有关。需要进一步研究来阐明 ACE2 和 Ang-(1-7) 的调节和作用机制。然而，RAS 中通过 ACE2 和 Ang-(1-7) 的第二个轴可能是心血管和代谢疾病治疗的重要靶点。
Recent studies have established a new regulatory axis in the renin–angiotensin system (RAS). In this axis, angiotensin (Ang)-(1–7) is finally produced from Ang I or Ang II by the catalytic activity of angiotensin-converting enzyme 2 (ACE2). Ang-(1–7) shows actions different from those of AT1 receptor stimulation, such as vasodilatation, natriuresis, anti-proliferation and an increase in the bradykinin–NO (nitric oxide) system. As the catalytic efficiency of ACE2 is approximately 400-fold higher with Ang II as a substrate than with Ang I, this axis is possibly acting as a counter-regulatory system against the ACE/Ang II/AT1 receptor axis. The signaling pathway of the ACE2–Ang-(1–7) axis has not yet been totally and clearly understood. However, a recent report suggests that the Mas oncogene acts as a receptor for Ang-(1–7). Intracellular signaling through Mas is not clear yet. Several factors such as Akt phosphorylation, protein kinase C activation and mitogen-activated protein (MAP) kinase inhibition seem to be involved in this signaling pathway. Further investigations are needed to clarify the regulation and mechanism of action of ACE2 and Ang-(1–7). However, this second axis through ACE2 and Ang-(1–7) in RAS can be an important target for the therapy of cardiovascular and metabolic disorders.
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