Role of the ACE2/Angiotensin 1-7 Axis of the Renin-Angiotensin System in Heart Failure.
Role of the ACE2/Angiotensin 1-7 Axis of the Renin-Angiotensin System in Heart Failure.
复制标题
肾素-血管紧张素系统的 ACE2/血管紧张素 1-7 轴在心力衰竭中的作用。
DOI：
10.1161/circresaha.116.307708
复制
发表时间：
2016-04-15
影响因子：
20.1
通讯作者：
Oudit GY
中科院分区：
文献类型：
--
作者：
Patel VB;Zhong JC;Grant MB;Oudit GY
在工业化国家，心力衰竭(HF)仍然是最常见的死亡和残疾原因，也是主要的经济负担。生理学、药理学和临床研究表明，肾素-血管紧张素系统的激活是心力衰竭进展的关键介质。血管紧张素转换酶2(ACE2)是血管紧张素转换酶(ACE)的同系物，是一种将血管紧张素II转化为血管紧张素-1-7(Ang 1-7)的单羧基肽酶，通过作用于Mas受体，对抗血管紧张素II的分子和细胞效应。ACE2广泛表达于心肌细胞、成纤维细胞和冠状动脉内皮细胞。最近的临床前翻译研究证实，ACE2/Ang1-7轴对激活的肾素-血管紧张素系统具有关键的反调节作用，导致射血分数保留的心衰。虽然ACE2的丢失增加了对HF的易感性，但增加ACE2水平可以防止和逆转HF的表型。血管紧张素转换酶2和血管紧张素转换酶1-7在减少和保留射血分数的情况下已成为对抗心衰的关键保护途径。重组人血管紧张素转换酶2已经在I期和II期临床试验中进行了测试，在降低和提高血浆血管紧张素II和血管紧张素-7水平的同时没有不良反应。本文讨论了ACE2的转录和转录后调节，以及ACE2/Ang 1-7轴在心脏生理学和心衰病理生理中的作用。强调了增强ACE2/Ang 1-7作用作为一种治疗心力衰竭的新疗法的药理和治疗潜力。
Heart failure (HF) remains the most common cause of death and disability, and a major economic burden, in industrialized nations. Physiological, pharmacological, and clinical studies have demonstrated that activation of the renin-angiotensin system is a key mediator of HF progression. Angiotensin-converting enzyme 2 (ACE2), a homolog of ACE, is a monocarboxypeptidase that converts angiotensin II into angiotensin 1-7 (Ang 1-7) which, by virtue of its actions on the Mas receptor, opposes the molecular and cellular effects of angiotensin II. ACE2 is widely expressed in cardiomyocytes, cardiofibroblasts, and coronary endothelial cells. Recent preclinical translational studies confirmed a critical counter-regulatory role of ACE2/Ang 1-7 axis on the activated renin-angiotensin system that results in HF with preserved ejection fraction. Although loss of ACE2 enhances susceptibility to HF, increasing ACE2 level prevents and reverses the HF phenotype. ACE2 and Ang 1-7 have emerged as a key protective pathway against HF with reduced and preserved ejection fraction. Recombinant human ACE2 has been tested in phase I and II clinical trials without adverse effects while lowering and increasing plasma angiotensin II and Ang 1-7 levels, respectively. This review discusses the transcriptional and post-transcriptional regulation of ACE2 and the role of the ACE2/Ang 1-7 axis in cardiac physiology and in the pathophysiology of HF. The pharmacological and therapeutic potential of enhancing ACE2/Ang 1-7 action as a novel therapy for HF is highlighted.