Department of Medicine, Austin Health, University of Melbourne Heidelberg, VIC, Australia.
Department of Medicine, Austin Health, University of Melbourne Heidelberg, VIC, Australia ; Department of Cardiology, Austin Health, University of Melbourne Heidelberg, VIC, Australia.
Front Physiol. 2014 Jun 24;5:227. doi: 10.3389/fphys.2014.00227. eCollection 2014.
Hypertension is a major risk factor for stroke, coronary events, heart and renal failure, and the renin-angiotensin system (RAS) plays a major role in its pathogenesis. Within the RAS, angiotensin converting enzyme (ACE) converts angiotensin (Ang) I into the vasoconstrictor Ang II. An "alternate" arm of the RAS now exists in which ACE2 counterbalances the effects of the classic RAS through degradation of Ang II, and generation of the vasodilator Ang 1-7. ACE2 is highly expressed in the heart, blood vessels, and kidney. The catalytically active ectodomain of ACE2 undergoes shedding, resulting in ACE2 in the circulation. The ACE2 gene maps to a quantitative trait locus on the X chromosome in three strains of genetically hypertensive rats, suggesting that ACE2 may be a candidate gene for hypertension. It is hypothesized that disruption of tissue ACE/ACE2 balance results in changes in blood pressure, with increased ACE2 expression protecting against increased blood pressure, and ACE2 deficiency contributing to hypertension. Experimental hypertension studies have measured ACE2 in either the heart or kidney and/or plasma, and have reported that deletion or inhibition of ACE2 leads to hypertension, whilst enhancing ACE2 protects against the development of hypertension, hence increasing ACE2 may be a therapeutic option for the management of high blood pressure in man. There have been relatively few studies of ACE2, either at the gene or the circulating level in patients with hypertension. Plasma ACE2 activity is low in healthy subjects, but elevated in patients with cardiovascular risk factors or cardiovascular disease. Genetic studies have investigated ACE2 gene polymorphisms with either hypertension or blood pressure, and have produced largely inconsistent findings. This review discusses the evidence regarding ACE2 in experimental hypertension models and the association between circulating ACE2 activity and ACE2 polymorphisms with blood pressure and arterial hypertension in man.
高血压是中风、冠心病、心肾衰竭的主要危险因素，肾素-血管紧张素系统（RAS）在其发病机制中起主要作用。在 RAS 中，血管紧张素转换酶（ACE）将血管紧张素（Ang）I 转化为血管收缩素 Ang II。RAS 的“替代”分支现在存在，其中 ACE2 通过降解 Ang II 和生成血管扩张素 Ang 1-7 来抵消经典 RAS 的作用。ACE2 在心脏、血管和肾脏中高度表达。ACE2 的催化活性外肽结构域发生脱落，导致循环中的 ACE2。ACE2 基因定位于三种遗传性高血压大鼠的 X 染色体上的一个数量性状位点，表明 ACE2 可能是高血压的候选基因。据推测，组织 ACE/ACE2 平衡的破坏会导致血压变化，ACE2 表达增加可预防血压升高，ACE2 缺乏会导致高血压。实验性高血压研究在心脏或肾脏和/或血浆中测量 ACE2，并报告 ACE2 的缺失或抑制会导致高血压，而增强 ACE2 可预防高血压的发生，因此增加 ACE2 可能是治疗高血压的一种选择。在高血压患者中，ACE2 的研究相对较少，无论是在基因水平还是在循环水平上。健康受试者的血浆 ACE2 活性较低，但心血管危险因素或心血管疾病患者的血浆 ACE2 活性升高。遗传研究已经调查了 ACE2 基因多态性与高血压或血压的关系，并得出了不一致的结果。这篇综述讨论了 ACE2 在实验性高血压模型中的证据，以及循环 ACE2 活性和 ACE2 多态性与人类血压和动脉高血压之间的关系。
