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

From National Research Council Canada

DOIResolve DOI: https://doi.org/10.1016/j.thromres.2007.03.024
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Name affiliation
  1. National Research Council of Canada. NRC Biotechnology Research Institute
FormatText, Article
Journal titleThrombosis Research
ISSN0049-3848
1879-2472
Volume121
Issue2
Pages203–212
Subjecttissue type plasminogen activator; vascular endothelial growth factor; fibrin degradation; metalloproteases
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.
Publication date
PublisherElsevier
LanguageEnglish
NRC numberNRC-BRI-47818
NPARC number3538641
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