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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.

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Autor(es)

Drouet, Christian -  Désormeaux, Anik -  Robillard, Josée -  Ponard, Denise -  Bouillet, Laurence -  Martin, Ludovic -  Kanny, Gisèle -  Moneret -  Vautrin, Denise -  Anne -  Bosson, Jean -  Luc -  Quesada, Jean -  Louis -  López -  Trascasa, Margarita -  Adam, Albert - 

Id.: 70446821

Idioma: inglés  - 

Versión: 1.0

Estado: Final

Palabras claveMESH  -  Adult - 

Tipo de recurso: info:eu-repo/semantics/article  -  Journal articles  - 

Tipo de Interactividad: Expositivo

Nivel de Interactividad: muy bajo

Audiencia: Estudiante  -  Profesor  -  Autor  - 

Estructura: Atomic

Coste: no

Copyright: sí

Requerimientos técnicos:  Browser: Any - 

Relación: [IsBasedOn] ISSN: 0091-6749
[IsBasedOn] Journal of Allergy and Clinical Immunology
[IsBasedOn] https://hal.archives-ouvertes.fr/hal-00281331
[IsBasedOn] Journal of Allergy and Clinical Immunology, Elsevier, 2008, 121 (2), pp.429-33. 〈10.1016/j.jaci.2007.10.048〉
[References] info:eu-repo/semantics/altIdentifier/doi/10.1016/j.jaci.2007.10.048
[References] info:eu-repo/semantics/altIdentifier/pmid/18158172

Fecha de contribución: 21-ene-2018

Contacto:

Localización:
* hal-00281331
* DOI : 10.1016/j.jaci.2007.10.048
* PUBMED : 18158172

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