title: Metallopeptidase activities in hereditary angioedema: effect of androgen prophylaxis on plasma aminopeptidase P.
abstract: 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.
  
  
  OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: GREPI/CNRS UMR 5525 and Université Joseph Fourier, Grenoble, France. CDrouet@chu-grenoble.fr
authors.forename: Christian
authors.initials: C
authors.lastname: Drouet
authors.forename: Anik
authors.initials: A
authors.lastname: Désormeaux
authors.forename: Josée
authors.initials: J
authors.lastname: Robillard
authors.forename: Denise
authors.initials: D
authors.lastname: Ponard
authors.forename: Laurence
authors.initials: L
authors.lastname: Bouillet
authors.forename: Ludovic
authors.initials: L
authors.lastname: Martin
authors.forename: Gisèle
authors.initials: G
authors.lastname: Kanny
authors.forename: Denise-Anne
authors.initials: DA
authors.lastname: Moneret-Vautrin
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Bosson
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Quesada
authors.forename: Margarita
authors.initials: M
authors.lastname: López-Trascasa
authors.forename: Albert
authors.initials: A
authors.lastname: Adam
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000626:Aminopeptidases / Q000097:blood*; D000728:Androgens / Q000627:therapeutic use*; D054179:Angioedemas, Hereditary / Q000097:blood* / Q000503:physiopathology / Q000517:prevention & control*; D050718:Complement C1 Inhibitor Protein / Q000378:metabolism; D006801:Humans; D007705:Kinins / Q000378:metabolism; D001121:Lysine Carboxypeptidase / Q000097:blood; D008660:Metabolism; D045726:Metalloproteases / Q000097:blood*; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D011446:Prospective Studies; D012720:Severity of Illness Index
chemical_list: D000728:Androgens; D050718:Complement C1 Inhibitor Protein; D007705:Kinins; D045726:Metalloproteases; D000626:Aminopeptidases; C022750:X-Pro aminopeptidase; D007703:Peptidyl-Dipeptidase A; D001121:Lysine Carboxypeptidase