Figure 4

The biology of angiotensin-converting enzyme (ACE) in tissue fibrosis. Angiotensin-converting enzyme has two catalytic sites. Angiotensin I exhibits higher affinity for the C-terminal catalytic site of ACE. Degradation of the antifibrotic molecule N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is exclusively induced at its N-terminal catalytic site. Therefore ACE induces tissue fibrosis by both the production of angiotensin II and the decreased level of AcSDKP. The ACE inhibitor captopril displays higher affinity for the N-terminal catalytic sites of ACE when compared to C-terminal catalytic sites. RXP407, a specific inhibitor for the ACE N-terminal catalytic site, may increase concentrations of AcSDKP and exhibit an antifibrotic action.