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

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• 作者：Christian Drouet ; Anik Dé ; sormeaux ; José ; e Robillard ; Denise Ponard ; Laurence Bouillet ; Ludovic Martin ; Gisè ; le Kanny ; Denise-Anne Moneret-Vautrin ; Jean-Luc Bosson ; Jean-Louis Quesada ; Margarita Ló ; pez-Trascasa ; Albert Adam
• 关键词：Hereditary angioedema ; aminopeptidase P ; C1 inhibitor ; androgen ; danazol ; stanozolol ; bradykinin ; des-Arg⁹-bradykinin
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2008
• 出版时间：February 2008
• 年：2008
• 卷：121
• 期：2
• 页码：429-433
• 全文大小：420 K

文摘

Background

Aminopeptidase P (APP) plays an important role in the catabolism of kinins in human plasma, mostly for des-Arg⁹-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 ≤ .001). Prophylaxis with androgen induced a significant increase in APP activity (P ≤ .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 ≤ .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.