Metallopeptidase activities in hereditary angioedema: effect of androgen prophylaxis on plasma aminopeptidase P

J Allergy Clin Immunol. 2008 Feb;121(2):429-33. doi: 10.1016/j.jaci.2007.10.048. Epub 2007 Dec 26.


Background: Aminopeptidase P (APP) plays an important role in the catabolism of kinins in human plasma, mostly for des-Arg(9)-bradykinin. Impaired degradation of this active bradykinin metabolite was found to be associated with a decreased APP activity in hypertensive patients who experienced angioedema while being treated with angiotensin I-converting enzyme inhibitors. The pathophysiology of hereditary angioedema is presently attributed only to a quantitative/qualitative C1 inhibitor (CI-INH) defect with increased bradykinin release.

Objectives: In the context of androgen prophylaxis, increased CI-INH function cannot fully explain protection from angioedema attacks alone because of the limited reversion of the CI-INH defects. Therefore we hypothesized that androgen prophylaxis could enhance plasma APP activity.

Methods: Patients with hereditary angioedema were investigated for plasma metallopeptidase activities responsible for kinin catabolism (APP, angiotensin I-converting enzyme, and carboxypeptidase N) and for CI-INH function in treated and untreated patients.

Results: APP activity was asymmetrically distributed in untreated patients (n = 147): the mean value was significantly lower than the value in a reference healthy and unmedicated population (n = 116; P < or = .001). Prophylaxis with androgen induced a significant increase in APP activity (P < or = .001), whereas it did not affect the other metallopeptidase activities. In both patient groups, APP activity showed a significant inverse relationship to disease severity (P < or = .001).

Conclusion: In addition to the effect on circulating CI-INH levels, the increase in APP levels brought on by androgens could contribute to a more effective control of the kinin accumulation considered to be responsible for the symptoms of angioedema.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aminopeptidases / blood*
  • Androgens / therapeutic use*
  • Angioedemas, Hereditary / blood*
  • Angioedemas, Hereditary / physiopathology
  • Angioedemas, Hereditary / prevention & control*
  • Complement C1 Inhibitor Protein / metabolism
  • Humans
  • Kinins / metabolism
  • Lysine Carboxypeptidase / blood
  • Metabolism
  • Metalloproteases / blood*
  • Middle Aged
  • Peptidyl-Dipeptidase A / blood
  • Prospective Studies
  • Severity of Illness Index


  • Androgens
  • Complement C1 Inhibitor Protein
  • Kinins
  • Metalloproteases
  • Aminopeptidases
  • X-Pro aminopeptidase
  • Peptidyl-Dipeptidase A
  • Lysine Carboxypeptidase