Metallopeptidase activities in hereditary angioedema: effect of androgen prophylaxis on plasma aminopeptidase P.
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.
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
D000728:Androgens; D050718:Complement C1 Inhibitor Protein; D007705:Kinins; D045726:Metalloproteases; D000626:Aminopeptidases; C022750:X-Pro aminopeptidase; D007703:Peptidyl-Dipeptidase A; D001121:Lysine Carboxypeptidase