Fig. 1.

Processing cascade for Angiotensin-(1-7). Renin cleaves angiotensinogen to angiotensin I (Ang I), which is further processed to the biologically active peptide Ang II by angiotensin-converting enzyme (ACE). Ang II undergoes further processing by the carboxypeptidase ACE2 to form Ang-(1-7). Ang-(1-7) is also formed through non-Ang II pathways by the direct processing of Ang I by the endopeptidases neprilysin (NEP) and thimet oligopeptidase (TOP). Ang-(1-7) is subsequently metabolized by ACE to Ang-(1-5), dipeptidyl peptidase 3 (DPP3) to Ang-(3-7) and Ang-(5-7), or by aminopeptidase A (APA) to Ang-(2-7). (Adapted from Chappell [89])