ACE۲/Ang-(۱-۷)/MAS axis effects on cardiovascular and renal system: A narrative review

Introduction: Classic Renin-Angiotensin System (RAS) activation may induce deleterious effects leading tovarious cardiovascular pathologies, such as hypertension, endothelial dysfunction, uncompensated heart failure,vasoconstriction, sodium and water retention, inflammation, fibrosis, and the generation of reactive oxidativespecies in kidney disease. Recent studies have unveiled a new member of RAS, Angiotensin-(۱-۷) [Ang-(۱-۷)],which exerts its influence via the Mas receptor and is synthesized by Angiotensin Converting Enzyme ۲ (ACE۲),utilizing Angiotensin II as a substrate to produce Ang-۱-۷.It has been demonstrated that Ang-(۱-۷) inhibits the ACE/ANGII/AT۱R axis, imparting antithrombotic,antifibrotic, anti-inflammatory, and antiproliferative effects. In this study, we conducted a literature review toinvestigate whether ANG-(۱-۷) exhibits discernible effects on renal and cardiovascular systems.Methods: We searched PubMed, selecting ۱۵۵ articles related to Ang-(۱-۷) and its effects on body systems. Ofthese, ۳۷ articles were relevant to our study, excluding ۴ articles that did not directly discuss the ACE۲/Ang-(۱-۷)/Mas axis.Results: Ang-(۱-۷), by inhibiting classic RAS, reduces the risk of atherosclerosis, diabetic neuropathy, andglomerulonephritis, possibly by blocking the fibrosis pathway and reducing TGF-beta. The ACE۲/Ang-(۱-۷)/Mas axis might significantly contribute to cardiovascular disease. Oral administration of Angiotensin ۱-۷,included in cyclodextrin [Ang-(۱-۷)-CyD], resulted in a reduction of infarcted areas of the heart. According tothese studies, it exerts this protective role by increasing the impact of bradykinin on coronary vessel dilation,reducing norepinephrine release, and regulating growth remodeling mediated through the Mas receptor via Gproteinsignaling.Conclusion: Angiotensin ۱-۷ exhibits inhibitory effects on the detrimental actions of Ang II. Throughexperiments conducted on rats, it demonstrated cardioprotective, anti-inflammatory, and anti-necrotic effects.Moreover, it displayed nephroprotective effects and played a role in the regulation of ions and electrolytes.

کلیدواژه ها:

Angiotensin-(۱-۷) ، renin-angiotensin-system ، Mas receptor ، Cardioprotective ، nephroprotective