ACE2-angiotensin-(1-7)-Mas axis and oxidative stress in cardiovascular disease.
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.
Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Luiza A
LA
Rabelo
Natalia
N
Alenina
Michael
M
Bader
D000803:Angiotensin I / Q000096:biosynthesis / Q000502:physiology*; D000085962:Angiotensin-Converting Enzyme 2; D002318:Cardiovascular Diseases / Q000209:etiology / Q000503:physiopathology*; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D019255:NADPH Oxidases / Q000378:metabolism / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D010446:Peptide Fragments / Q000096:biosynthesis / Q000502:physiology*; D007703:Peptidyl-Dipeptidase A / Q000502:physiology*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013481:Superoxides / Q000378:metabolism
D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D013481:Superoxides; D009569:Nitric Oxide; D000803:Angiotensin I; D019255:NADPH Oxidases; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7)