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

Autor: Samira Mihoubi, Edith Beaulieu, Denis Gingras, Richard Béliveau, David Ratel, Yves Durocher, Georges-Etienne Rivard
Přispěvatelé: Laboratoire de Médecine Moléculaire Ste-Justine-UQAM, Centre de Cancérologie Charles-Bruneau, Hôpital Ste-Justine-Université du Québec à Montréal = University of Québec in Montréal (UQAM), Animal Cell Technology Group, National Research Council Canada-Biotechnology Research Institute, Service d'Hématologie-Oncologie, Hôpital Ste-Justine, This work was supported by a grant from the Canadian Institutes for Health Research to D.G. and R.B., Issartel, Jean-Paul
Rok vydání: 2007
Předmět:
Vascular Endothelial Growth Factor A
MESH: Matrix Metalloproteinases
Angiogenesis
Plasmin
medicine.medical_treatment
Matrix metalloproteinase
metalloproteases
MESH: Fibrinolysis
0302 clinical medicine
MESH: Tissue Plasminogen Activator
MESH: Up-Regulation
MESH: Angiogenesis Inducing Agents
MESH: Endothelial Cells
MESH: Fibrin
Cells
Cultured
0303 health sciences
vascular endothelial growth factor
biology
Chemistry
Fibrinolysis
tissue type plasminogen activator
Hematology
Up-Regulation
Cell biology
Endothelial stem cell
Tissue Plasminogen Activator
030220 oncology & carcinogenesis
MESH: Endothelium
Vascular
MESH: Neovascularization
Physiologic
MESH: Cells
Cultured
medicine.drug
Neovascularization
Physiologic
Fibrin
03 medical and health sciences
[SDV.BBM] Life Sciences [q-bio]/Biochemistry
Molecular Biology
medicine
Humans
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology
030304 developmental biology
MESH: Humans
MESH: Vascular Endothelial Growth Factor Receptor-2
T-plasminogen activator
MESH: Vascular Endothelial Growth Factor A
Endothelial Cells
Vascular Endothelial Growth Factor Receptor-2
Matrix Metalloproteinases
Immunology
biology.protein
Angiogenesis Inducing Agents
Endothelium
Vascular
Plasminogen activator
fibrin degradation
Zdroj: Thrombosis Research
Thrombosis Research, Elsevier, 2007, 121 (2), pp.203-12. ⟨10.1016/j.thromres.2007.03.024⟩
ISSN: 0049-3848
1879-2472
DOI: 10.1016/j.thromres.2007.03.024
Popis: International audience; 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.
Databáze: OpenAIRE
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