Abstract
The Renin angiotensin system (RAS) is an intricate pathway that regulates homeostasis. The proliferative arm of RAS that includes angiotensin converting enzyme (ACE), angiotensin II (Ang II), and angiotensin II type 1 receptor (AT1R) contributes to pathophysiological responses such as vasoconstriction, hypertension, and cardiovascular, cerebral, and renal complications. The discovery of angiotensin converting enzyme 2 (ACE 2), the analog of ACE, synthesizes angiotensin (1-7) [Ang (1-7)] from Ang II or even from angiotensin I (Ang I) or angiotensin (1-9) [Ang (1-9)] less efficiently. Ang (1-7) is a biologically active peptide, also the endogenous antagonist of Ang II, and opposes the derogatory activities of the conventional axis of RAS. The functional binding site for Ang (1-7) is a G protein-coupled, AT1R and Mas receptor. ACE 2/Ang (1-7)/Mas is therefore termed the non-conventional axis of RAS, which is an endogenous counter-regulatory arm within RAS against the conventional axis. In conclusion, the ACE2/Ang (1-7)/Mas axis is the protective component of the renin-angiotensin system, counteracting the effects of angiotensin II and supporting cardiovascular and renal health. However, the detailed molecular mechanism of RAS as a whole still remains elusive due to the fact that RAS is highly organ, gender, and species/strain-specific, and much focus is needed in this area.
This review examines the non-conventional RAS axis, focusing on its impact on cardiovascular and renal systems, metabolism, and its potential interactions with AT1R, angiotensin II type 1 receptor (AT2R), and Mas. Evidence suggests that enhancing the ACE 2/Ang (1-7)/Mas axis can improve outcomes in diseases related to RAS dysregulation, highlighting its promise as a therapeutic target for cardiovascular and renal conditions. Additionally, the review explores how leveraging the ACE 2/Ang (1-7)/Mas axis could lead to new pharmacological treatments for hypertension and related cardiovascular, renal, cerebral, and metabolic syndromes.
Keywords
RAS, Ang II, Ang 1-7, ACE, ACE 2, AT1R, AT2R, Mas receptor