Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
Clin Sci (Lond). 2013 Jan;124(2):65-76. doi: 10.1042/CS20120269.
The RAS (renin-angiotensin system) plays an important role in the pathophysiology of CVD (cardiovascular disease), and RAS blockade is an important therapeutic strategy in the management of CVD. A new counterbalancing arm of the RAS is now known to exist in which ACE (angiotensin-converting enzyme) 2 degrades Ang (angiotensin) II, the main effector of the classic RAS, and generates Ang-(1-7). Altered ACE2 expression is associated with cardiac and vascular disease in experimental models of CVD, and ACE2 is increased in failing human hearts and atherosclerotic vessels. In man, circulating ACE2 activity increases with coronary heart disease, as well as heart failure, and a large proportion of the variation in plasma ACE2 levels has been attributed to hereditary factors. The ACE2 gene maps to chromosome Xp22 and this paper reviews the evidence associating ACE2 gene variation with CVD and considers clues to potential functional ACE2 variants that may alter gene expression or transcriptional activity. Studies to date have investigated ACE2 gene associations in hypertension, left ventricular hypertrophy and coronary artery disease, but the results have been inconsistent. The discrepancies may reflect the sample size of the studies, the gender or ethnicity of subjects, the cardiovascular phenotype or the ACE2 SNP investigated. The frequent observation of apparent sex-dependence might be of special importance, if confirmed. As yet, there are no studies to concurrently assess ACE2 gene polymorphisms and circulating ACE2 activity. Large-scale carefully conducted clinical studies are urgently needed to clarify more precisely the potential role of ACE2 in the CVD continuum.
RAS（肾素-血管紧张素系统）在 CVD（心血管疾病）的病理生理学中发挥着重要作用，RAS 阻断是 CVD 管理中的重要治疗策略。现在已知 RAS 存在一个新的平衡臂，其中 ACE（血管紧张素转换酶）2 降解 Ang（血管紧张素）II，这是经典 RAS 的主要效应物，并生成 Ang-（1-7）。在 CVD 的实验模型中，改变 ACE2 的表达与心脏和血管疾病有关，并且在衰竭的人心和动脉粥样硬化血管中 ACE2 增加。在人类中，循环 ACE2 活性随着冠心病以及心力衰竭而增加，并且血浆 ACE2 水平的大部分变化归因于遗传因素。ACE2 基因位于 Xp22 染色体上，本文综述了 ACE2 基因变异与 CVD 相关的证据，并考虑了潜在功能性 ACE2 变体的线索，这些变体可能改变基因表达或转录活性。迄今为止，已有研究调查了 ACE2 基因与高血压、左心室肥厚和冠状动脉疾病的相关性，但结果不一致。差异可能反映了研究的样本量、受试者的性别或种族、心血管表型或研究的 ACE2 SNP。如果得到证实，经常观察到明显的性别依赖性可能具有特殊意义。到目前为止，还没有研究同时评估 ACE2 基因多态性和循环 ACE2 活性。迫切需要进行大规模的精心临床研究，以更准确地阐明 ACE2 在 CVD 连续体中的潜在作用。
