Ferrara, Anne Lise (2020) Role of Vasoactive Mediators in Hereditary Angioedema. [Tesi di dottorato]


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Item Type: Tesi di dottorato
Lingua: English
Title: Role of Vasoactive Mediators in Hereditary Angioedema
Ferrara, Anne Liseanneliseferrara@gmail.com
Date: 6 March 2020
Number of Pages: 67
Institution: Università degli Studi di Napoli Federico II
Department: Scienze Mediche Traslazionali
Dottorato: Medicina clinica e sperimentale
Ciclo di dottorato: 32
Coordinatore del Corso di dottorato:
Beguinot, Francescobeguino@unina.it
Date: 6 March 2020
Number of Pages: 67
Uncontrolled Keywords: Angiopoietin (ANGPT); Vascular Endothelial Growth Factor (VEGF); Leakage
Settori scientifico-disciplinari del MIUR: Area 06 - Scienze mediche > MED/09 - Medicina interna
Date Deposited: 26 Mar 2020 12:27
Last Modified: 10 Nov 2021 14:30
URI: http://www.fedoa.unina.it/id/eprint/13015


Hereditary angioedema is a disabling, life-threatening condition caused by deficiency (type I) or dysfunction (type II) of the C1 inhibitor protein (C1-INH-HAE), mutation of genes encoding Factor XII (FXII-HAE), Angiopoietin-1 (ANGPT1-HAE) or by unknown factors (U-HAE) leading to bradykinin accumulation and recurrent episodes of edema attack. Vascular leakage is a complex process sustained by the coordinated production of several permeabilizing factors. It has been demonstrated the implication of Vascular Endothelial Growth Factors (VEGFs), Angiopoietins (ANGPTs), Secreted phospholipases A2 (sPLA2) and Platelet Activating Factor-Acetylhydrolase (PAF-AH) in vascular permeabilization. In this study, we sought to analyze plasma levels of these mediators in C1-INH-HAE during remission and angioedema attack and in FXII-HAE, ANGPT1-HAE and U-HAE patients during remission phase. Plasma concentrations of VEGF-A, VEGF-C, ANGPT1 and ANGPT2 and enzymatic activities of sPLA2 and PAF-AH are increased in patients with C1-INH-HAE during remission compared to healthy controls. In addition, FXII-HAE patients reported altered concentrations of VEGFA whereas U-HAE patients of VEGF-A, VEGF-C and ANGPT1. By contrast, no alteration of these mediators was found in ANGPT1-HAE. VEGF-A and VEGF-C concentrations were not altered during attack compared to remission. By contrast, enzymatic activities of sPLA2 and PAF-AH are decreased. Concentrations of ANGPT1, a vascular stabilizer, were increased during attacks compared to symptoms-free periods, whereas ANGPT2 levels were not altered. In addition, nailfold video-capillaroscopy revealed structural and morphological alterations of capillaries of C1-INH-HAE patients. Our results emphasize the complexity by which several vasoactive mediators are involved not only in the pathophysiology of C1-INH-HAE, but also during angioedema attacks and its resolution.


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