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

Abstract Significance: 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, regula...