Role of ACE2 in diastolic and systolic heart failure
Role of ACE2 in diastolic and systolic heart failure
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DOI：
10.1007/s10741-011-9259-x
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发表时间：
2012-09-01
影响因子：
4.6
通讯作者：
Oudit, Gavin Y.
中科院分区：
文献类型：
--
作者：
Wang, Wang;Bodiga, Sreedhar;Oudit, Gavin Y.
ACE 2是一种新型的血管紧张素转换酶（ACE）同系物，是一种代谢多种肽的单羧肽酶。ACE 2降解血管紧张素（Ang）II（一种具有血管收缩/增殖作用的肽）以产生Ang-（1-7），其通过其受体Mas发挥血管舒张/抗增殖作用。此外，由于ACE 2是一种多功能酶，其对其他血管活性肽的作用也有助于其血管活性作用，包括apelin-13和apelin-17肽。ACE 2的发现证实了在肾素-血管紧张素系统内建立了两个反调节臂。第一条臂由ACE-Ang Ⅱ-AT（1）受体轴参与的经典途径形成，第二条臂由ACE 2-Ang 1-7/Mas受体轴构成。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。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。ACE 2-Ang 1-7/Mas轴可能代表开发用于治疗高血压和心血管疾病的新治疗策略的新可能性。在这篇综述中，我们将总结ACE 2的生化和病理生理方面的重点是其在舒张性和收缩性心力衰竭中的作用。
A novel angiotensin-converting enzyme (ACE) homolog, named ACE2, is a monocarboxypeptidase which metabolizes several peptides. ACE2 degrades Angiotensin (Ang) II, a peptide with vasoconstrictive/proliferative effects, to generate Ang-(1-7), which acting through its receptor Mas exerts vasodilatory/anti-proliferative actions. In addition, as ACE2 is a multifunctional enzyme and its actions on other vasoactive peptides can also contribute to its vasoactive effects including the apelin-13 and apelin-17 peptides. The discovery of ACE2 corroborates the establishment of two counter-regulatory arms within the renin-angiotensin system. The first one is formed by the classical pathway involving the ACE-Ang II-AT(1) receptor axis and the second arm is 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. ACE2 is also a negative regulator of Ang II-induced myocardial hypertrophy, fibrosis, and diastolic dysfunction. The ACE2-Ang 1-7/Mas axis may represent new possibilities for developing novel therapeutic strategies for the treatment of hypertension and cardiovascular diseases. In this review, we will summarize the biochemical and pathophysiological aspects of ACE2 with a focus on its role in diastolic and systolic heart failure.