FIGURE 1.

Schematic representation of the renin-angiotensin system (RAS) showing that the angiotensin converting enzyme 2 (ACE2)/Angiotensin-(1–7)/Mas receptor axis exerts opposite effects to those of ACE/Angiotensin II/AT1 receptor axis. Renin cleaves hepatic angiotensinogen into Angiotensin I which is then cleaved via ACE into Angiotensin II. The effects of Angiotensin II are exerted mainly through the activation of the Angiotensin II type 1 receptor (AT1R) and includes vasoconstriction, inflammation, fibrosis, oxidative stress and cell growth. Angiotensin II also binds to Angiotensin II type 2 receptor (AT2R) which usually opposes the actions of AT1R. Angiotensin-(1–7), which is a specific Mas receptor (MasR) agonist, can be formed directly from Angiotensin II via ACE2, or it can be generated through the ACE2-catalyzed hydrolysis of Angiotensin I to the inactive Angiotensin-(1–9) which is then converted to Angiotensin-(1–7) by ACE or neprilysin (NEP). However, Angiotensin-(1–7) is mainly formed through the action of ACE2 on Angiotensin II which has more affinity to ACE2 than Angiotensin I. When levels of Ang II are not sufficiently elevated, Ang-(1–7) can also be formed directly from Ang I via NEP. Interaction of Angiotensin-(1–7) with MasR triggers intracellular signaling pathways leading to beneficial actions such as vasodilation, anti-inflammatory, anti-fibrotic and anti-oxidative effects, and inhibition of cell proliferation.