(A) The RAS cascade showing the angiotensin peptide metabolic pathway. Angiotensinogen, as the starting substrate, is cleaved by renin to Ang I. Ang I is cleaved by ACE to Ang II, which is cleaved by ACE2 to Ang 1–7. Ang II acts on AT1 and AT2 receptors. Ang 1–7 acts on Mas receptors and counterbalances the Ang II/AT1R actions. (B) Decreased ACE2 shifts the balance in the RAS to the Ang II/AT1R axis, resulting in disease progression. Increased ACE2 (by rhACE2, gene delivery, or ACE2 activators) shifts the balance to the Ang 1–7/MasR axis, leading to protection from disease.