Angiotensin-Converting Enzyme Inhibitor-Associated Angioedema: From Bed to Bench.

BACKGROUND AND OBJECTIVE: Angiotensin-converting enzyme inhibitor-associated angioedema (ACEI-AAE) affects 0.1%-0.7% of patients treated with ACEIs. While previous research suggests that angioedema attacks result from increased vascular permeability, the pathogenesis is not completely understood. Objective: This study aimed to describe the clinical, genetic, and laboratory parameters of ACEI-AAE patients and to investigate the role of vascular endothelial growth factors A and C (VEGF-A and VEGF-C), angiopoietins 1 and 2 (Ang1/Ang2), and secretory phospholipase A2 (sPLA2) in the pathogenesis of ACEI-AAE. METHODS: The clinical and laboratory data of ACEI-AAE patients were collected from 2 angioedema reference centers. Healthy volunteers and ACEI-treated patients without angioedema were enrolled to compare laboratory parameters. Genetic analyses to detect mutations in the genes SERPING1, ANGPT1, PLG, and F12 were performed in a subset of patients. RESULTS: A total of 51 patients (57% male) were diagnosed with ACEI-AAE. The average time to onset of symptoms from the start of ACEI therapy was 3 years (range, 30 days-20 years). The most commonly affected sites were the lips (74.5%), tongue (51.9%), and face (41.2%). Switching from ACEIs to sartans was not associated with an increased risk of angioedema in patients with a history of ACEIAAE. VEGF-A, VEGF-C, and sPLA2 plasma levels were higher in ACEI-AAE patients than in the controls. Ang1/2 concentrations remained unchanged. No mutations were detected in the genes analyzed. CONCLUSIONS: Our data suggest that sartans are a safe therapeutic alternative in ACEI-AAE patients. Increased concentrations of VEGF-A, VEGF-C, and sPLA2 in ACEI-AAE patients suggest a possible role of these mediators in the pathogenesis of ACEI-AAE.

Angiotensin-converting enzyme inhibitor-associated angioedema: from bed to bench

BACKGROUND: Angiotensin-converting enzyme inhibitor-associated angioedema (ACEI-AAE) affects 0.1%-0.7% of patients treated with ACEIs. While previous research suggests that angioedema attacks result from increased vascular permeability, the pathogenesis is not completely understood. OBJECTIVE: This study aimed to describe the clinical, genetic, and laboratory parameters of ACEI-AAE patients and to investigate the role of vascular endothelial growth factors A and C (VEGF-A and VEGF-C), angiopoietins 1 and 2 (Ang1/Ang2), and secretory phospholipase A2 (sPLA2) in the pathogenesis of ACEI-AAE. METHODS: The clinical and laboratory data of ACEI-AAE patients were collected from 2 angioedema reference centers. Healthy volunteers and ACEI-treated patients without angioedema were enrolled to compare laboratory parameters. Genetic analyses to detect mutations in the genes SERPING1, ANGPT1, PLG, and F12 were performed in a subset of patients. RESULTS: A total of 51 patients (57% male) were diagnosed with ACEI-AAE. The average time to onset of symptoms from the start of ACEI therapy was 3 years (range, 30 days-20 years). The most commonly affected sites were the lips (74.5%), tongue (51.9%), and face (41.2%). Switching from ACEIs to sartans was not associated with an increased risk of angioedema in patients with a history of ACEIAAE. VEGF-A, VEGF-C, and sPLA2 plasma levels were higher in ACEI-AAE patients than in the controls. Ang1/2 concentrations remained unchanged. No mutations were detected in the genes analyzed. CONCLUSIONS: Our data suggest that sartans are a safe therapeutic alternative in ACEI-AAE patients. Increased concentrations of VEGF-A, VEGF-C, and sPLA2 in ACEI-AAE patients suggest a possible role of these mediators in the pathogenesis of ACEI-AAE

ANTECEDENTES: El angioedema asociado al consumo de inhibidores de la enzima convertidora de angiotensina (IECA-AAE) ocurre en el 0,1%-0,7% de los pacientes tratados con IECA. Aunque se sugiere que los ataques de angioedema son el resultado de una mayor permeabilidad vascular, la patogénesis de este proceso no está plenamente esclarecida. OBJETIVO: En este trabajo se estudiaron los parámetros clínicos, genéticos y de laboratorio de pacientes con IECA-AAE, así como el papel de los factores de crecimiento endotelial vascular A y C (VEGF-A y VEGF-C), las angiopoyetinas 1 y 2 (Ang1/Ang2) y la fosfolipasa secretora A2 (sPLA2). MÉTODOS: Se recogieron datos clínicos y de laboratorio de pacientes con IECA-AAE procedentes de dos centros de referencia en angioedema. Se utilizaron pacientes control, que incluyeron a voluntarios sanos y a pacientes tratados con IECA sin angioedema, para comparar las concentraciones de los parámetros de laboratorio. Finalmente, se realizó un análisis genético en un subconjunto de pacientes para detectar mutaciones en los genes SERPING1, ANGPT1, PLG y F12. RESULTADOS: Se diagnosticaron a 51 pacientes (57% hombres) con IECA-AAE. El tiempo promedio para el inicio de los síntomas desde el comienzo del tratamiento con IECA fue de 3 años (rango de 30 días a 20 años). Los lugares más comúnmente afectados fueron: labios (74,5%), lengua (51,9%) y cara (41,2%). El cambio de IECA a ARA-II no se asoció con un mayor riesgo de angioedema en pacientes con antecedentes de IECA-AAE. Los niveles plasmáticos de VEGF-A, VEGF-C y sPLA2 fueron más altos en pacientes con IECA-AAE que en los controles. No se detectaron cambios en las concentraciones de Ang1/Ang2, ni se detectaron mutaciones en los genes analizados. CONCLUSIONES: Nuestros datos sugieren que los ARA-II pueden ser una alternativa terapéutica segura en pacientes con IECA-AAE. El aumento de las concentraciones de VEGF-A, VEGF-C y sPLA2 en pacientes con ACEI-AAE sugiere un posible papel de estos mediadores en la patogénesis de esta enfermedad