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Antioxid Redox Signal. 2017 Apr 20;26(12):645-659. doi: 10.1089/ars.2016.6950. Epub 2017 Jan 12.

ACE2 and the Homolog Collectrin in the Modulation of Nitric Oxide and Oxidative Stress in Blood Pressure Homeostasis and Vascular Injury.

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1 Department of Nephrology, Medical Faculty, Heinrich-Heine University Düsseldorf , Düsseldorf, Germany .
2 Division of Nephrology, Department of Medicine, University of Virginia , Charlottesville, Virginia.
3 Department of Internal Medicine, Graduate Institute of Biomedical and Pharmaceutical Science, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan .



Hypertension is the leading risk factor causing mortality and morbidity worldwide. Angiotensin (Ang) II, the most active metabolite of the renin-angiotensin system, plays an outstanding role in the pathogenesis of hypertension and vascular injury. Activation of angiotensin converting enzyme 2 (ACE2) has shown to attenuate devastating effects of Ang II in the cardiovascular system by reducing Ang II degradation and increasing Ang-(1-7) generation leading to Mas receptor activation. Recent Advances: Activation of the ACE2/Ang-(1-7)/Mas receptor axis reduces hypertension and improves vascular injury mainly through an increased nitric oxide (NO) bioavailability and decreased reactive oxygen species production. Recent studies reported that shedding of the enzymatically active ectodomain of ACE2 from the cell surface seems to regulate its activity and serves as an interorgan communicator in cardiovascular disease. In addition, collectrin, an ACE2 homolog with no catalytic activity, regulates blood pressure through an NO-dependent mechanism.


Large body of experimental data confirmed sustained beneficial effects of ACE2/Ang-(1-7)/Mas receptor axis activation on hypertension and vascular injury. Experimental studies also suggest that activation of collectrin might be beneficial in hypertension and endothelial dysfunction. Their role in clinical hypertension is unclear as selective and reliable activators of both axes are not yet available.


This review will highlight the results of recent research progress that illustrate the role of both ACE and collectrin in the modulation of NO and oxidative stress in blood pressure homeostasis and vascular injury, providing evidence for the potential therapeutic application of ACE2 and collectrin in hypertension and vascular disease. Antioxid. Redox Signal. 26, 645-659.


angiotensin converting enzyme 2; angiotensin-(1–7); apelin; blood pressure; collectrin; hypertension; oxidative stress; reactive oxygen species; renin–angiotensin system; vascular injury

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