Patel Vaibhav B, Putko Brendan, Wang Zuocheng, Zhong Jiu-Chang, Oudit Gavin Y
Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Canada.
Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Canada.
Drug Discov Today Ther Strateg. 2012 Winter;9(4):e141-e148. doi: 10.1016/j.ddstr.2013.11.001. Epub 2014 Jan 24.
Angiotensin converting enzyme 2 (ACE2), is a monocarboxypeptidase which metabolizes several peptides including the degradation of Ang II, a peptide with vasoconstrictive/proliferative/effects, to generate Ang 1-7, which acting through its receptor Mas exerts vasodilatory/anti-proliferative actions. The classical pathway of the RAS involving the ACE-Ang II-AT receptor axis is antagonized by the second arm constituted by the ACE2-Ang 1-7/Mas receptor axis. Loss of ACE2 enhances the adverse pathological remodeling susceptibility to pressure-overload and myocardial infarction. Human recombinant ACE2 is also a negative regulator of Ang II-induced myocardial hypertrophy, fibrosis and diastolic dysfunction and suppresses pressure-overload induced heart failure. Due to its characteristics, the ACE2-Ang 1-7/Mas axis may represent new possibilities for developing novel therapeutic strategies for the treatment of heart failure. Human recombinant ACE2 has been safely administered to healthy human volunteers intravenously resulting in sustained lowering of plasma Ang II levels. In this review, we will summarize the beneficial effects of ACE2 in heart disease and the potential use of human recombinant ACE2 as a novel therapy for heart failure.
血管紧张素转换酶2（ACE2）是一种单羧肽酶，可代谢多种肽，包括降解具有血管收缩/增殖/效应的肽血管紧张素II（Ang II），生成血管紧张素1-7（Ang 1-7），后者通过其受体Mas发挥血管舒张/抗增殖作用。肾素-血管紧张素系统（RAS）的经典途径涉及ACE-Ang II-AT受体轴，由ACE2-Ang 1-7/Mas受体轴构成的第二条途径对其起拮抗作用。ACE2的缺失会增加压力超负荷和心肌梗死导致的不良病理重塑易感性。人重组ACE2也是Ang II诱导的心肌肥大、纤维化和舒张功能障碍的负调节因子，并可抑制压力超负荷诱导的心力衰竭。由于其特性，ACE2-Ang 1-7/Mas轴可能为开发治疗心力衰竭的新型治疗策略带来新的可能性。人重组ACE2已被安全地静脉注射给健康人类志愿者，导致血浆Ang II水平持续降低。在本综述中，我们将总结ACE2在心脏病中的有益作用以及人重组ACE2作为心力衰竭新型治疗方法的潜在用途。
