ACE2–angiotensin-(1–7)–Mas axis and oxidative stress in cardiovascular disease

Abstract

The renin-angiotensin-aldosterone system (RAAS) is a pivotal regulator of physiological homeostasis and diseases of the cardiovascular system. Recently, new factors have been discovered, such as angiotensin-converting enzyme 2 (ACE2), angiotensin-(1-7) and Mas. This newly defined ACE2-angiotensin-(1-7)-Mas axis was shown to have a critical role in the vasculature and in the heart, exerting mainly protective effects. One important mechanism of the classic and the new RAAS regulate vascular function is through the regulation of redox signaling. Angiotensin II is a classic prooxidant peptide that increases superoxide production through the activation of NAD(P)H oxidases. This review summarizes the current knowledge about the ACE2-angiotensin-(1-7)-Mas axis and redox signaling in the context of cardiovascular regulation and disease. By interacting with its receptor Mas, angiotensin-(1-7) induces the release of nitric oxide from endothelial cells and thereby counteracts the effects of angiotensin II. ACE2 converts angiotensin II to angiotensin-(1-7) and, thus, is a pivotal regulator of the local effects of the RAAS on the vessel wall. Taken together, the ACE2-angiotensin-(1-7)-Mas axis emerges as a novel therapeutic target in the context of cardiovascular and metabolic diseases.

Olmesartan improves endothelial function in hypertensive patients: link with extracellular superoxide dismutase

“…ACE2 converts Ang II to angiotensin-1-7 (Ang- (1-7)), which increased NO release from endothelial cells through its receptor Mas, thus resulting in vasodilation. 32 As olmesartan reportedly increased aortic ACE2 and Ang-(1-7) in conjunction with improved vascular remodeling in spontaneously hypertensive rats, 33 the effect of olmesartan on endothelial function might be mediated by this pathway. In the present study, olmesartan significantly improved endothelial function as compared with baseline and amlodipine (Table 3).…”

Possible Role of Angiotensin-Converting Enzyme 2 and Activation of Angiotensin II Type 2 Receptor by Angiotensin-(1–7) in Improvement of Vascular Remodeling by Angiotensin II Type 1 Receptor Blockade

“…5 One important mechanism of vascular remodeling is via oxidative stress induced by the ACE/Ang II/AT 1 receptor axis, and the ACE2/Ang-(1-7)/Mas axis has also been reported to be involved in the regulation of oxidative stress. 19 For instance, it has been reported that MasKO mice from 2 different genetic backgrounds showed a reduction in superoxide dismutase and catalase activity, suggesting impaired antioxidant properties in these animals. 20 In addition, it is reported that the vasoprotective and atheroprotective effects of Ang-(1-7) are mediated by the restoration of nitric oxide bioavailability in apolipoprotein E-deficient mice.…”

New Components of the Renin-Angiotensin-Aldosterone System and Oxidative Stress

“…ACE2 promoted capillary and neovessel maturation and reduced atherosclerosis, and attenuated AngⅡ-induced reactive oxygen production in part through decreasing the expression of p22 phox in an Ang-(1-7)-dependent fashion. And we would like to refer details to reviews that report the relationship ACE2/ Ang-(1-7)/Mas Axis with oxidative stress [46,47]. Interactions between AT 1 receptor, Mas and NAD(P)H oxidase at signal transduction level from above mentioned reports [43] are summerized in Figure 2.…”