Under normal conditions, ACE is responsible for degrading bradykinin and substance P. However, when ACE activity is inhibited, aminopeptidase P (APP) takes over and inactivates bradykinin, while dipeptidyl peptidase-IV (DPP-IV) inactivates substance P. Inhibition of bradykinin and substance P degradation can lead to angioedema by causing plasma extravasation into the submucosal tissue (Figure 2) [19]. This evidence concerns the gene APP and angioedema.