Manipulating angiotensin metabolism with angiotensin converting enzyme 2 (ACE2) in heart failure.
Manipulating angiotensin metabolism with angiotensin converting enzyme 2 (ACE2) in heart failure.
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DOI：
10.1016/j.ddstr.2013.11.001
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发表时间：
2012-01-01
期刊：
影响因子：
--
通讯作者：
Oudit, Gavin Y
中科院分区：
文献类型：
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作者：
Patel, Vaibhav B;Putko, Brendan;Oudit, Gavin Y
血管紧张素转化酶2（ACE 2）是一种单羧肽酶，其代谢几种肽，包括降解具有血管收缩/增殖/作用的肽Ang II以产生Ang 1-7，其通过其受体Mas发挥血管舒张/抗增殖作用。涉及ACE-Ang II-AT 1受体轴的RAS经典途径被ACE 2-Ang 1-7/Mas受体轴构成的第二臂拮抗。ACE 2的缺失增强了对压力超负荷和心肌梗死的不良病理性重构易感性。人重组ACE 2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剂，并抑制压力超负荷诱导的心力衰竭。ACE 2-Ang 1-7/Mas轴可能代表开发心力衰竭治疗新策略的新可能性。人重组ACE 2已安全地静脉内给予健康的人类志愿者，导致血浆Ang II水平持续降低。本文综述了ACE 2在心脏病中的有益作用以及重组人ACE 2作为心力衰竭治疗新方法的潜在应用。
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-AT1 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.