VEGF increases the fibrinolytic activity of endothelial cells within fibrin matrices: involvement of VEGFR-2, tissue type plasminogen activator and matrix metalloproteinases.

Abstract : Proteolysis of fibrin matrices by endothelial cells plays essential roles in the migratory and morphogenic differentiation processes underlying angiogenesis. Using an in vitro fibrinolysis model consisting of human umbilical vein endothelial cells (HUVECs) embedded in a three dimensional fibrin matrix, we show that VEGF, an angiogenic cytokine that plays a crucial role in the onset of angiogenesis, is a potent activator of HUVEC-mediated fibrinolysis. This VEGF-dependent fibrin degradation was completely abrogated by inhibitors of either the plasminogen activator/plasmin or matrix metalloproteinases (MMP) proteolytic systems, suggesting the involvement of both classes of proteases in fibrin degradation. Accordingly, VEGF-induced fibrinolysis correlated with an increase in the expression of tPA and of some MMPs, such as MT2-MMP and was completely blocked by a neutralizing antibody against tPA. Overall, these results indicate that efficient proteolysis of three dimensional fibrin matrices during VEGF-mediated angiogenesis involves a complex interplay between the MMP and plasmin-mediated proteolytic systems.
Type de document :
Article dans une revue
Thrombosis Research, Elsevier, 2007, 121 (2), pp.203-12. 〈10.1016/j.thromres.2007.03.024〉
Liste complète des métadonnées

Littérature citée [36 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-00383800
Contributeur : Jean-Paul Issartel <>
Soumis le : vendredi 3 juillet 2009 - 14:45:07
Dernière modification le : jeudi 11 janvier 2018 - 02:37:14
Document(s) archivé(s) le : jeudi 10 juin 2010 - 23:06:43

Fichier

29F16A2Ed01.pdf
Fichiers produits par l'(les) auteur(s)

Identifiants

Collections

Citation

David Ratel, Samira Mihoubi, Edith Beaulieu, Yves Durocher, Georges-Etienne Rivard, et al.. VEGF increases the fibrinolytic activity of endothelial cells within fibrin matrices: involvement of VEGFR-2, tissue type plasminogen activator and matrix metalloproteinases.. Thrombosis Research, Elsevier, 2007, 121 (2), pp.203-12. 〈10.1016/j.thromres.2007.03.024〉. 〈inserm-00383800〉

Partager

Métriques

Consultations de la notice

342

Téléchargements de fichiers

294