Vascular Endothelial Growth Factor Enhances the Expression of Urokinase Receptor in Human Endothelial Cells via Protein Kinase C Activation

Marielle E. Kroon; Pieter Koolwijk; Mario A. Vermeer; Bea van der Vecht; Victor W. M. van Hinsbergh

doi:10.1055/s-0037-1615683

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2001; 85(02): 296-302
DOI: 10.1055/s-0037-1615683

Review Article

Schattauer GmbH

Vascular Endothelial Growth Factor Enhances the Expression of Urokinase Receptor in Human Endothelial Cells via Protein Kinase C Activation

Marielle E. Kroon

¹Gaubius Laboratory TNO-PG, Leiden, The Netherlands

,

Pieter Koolwijk

¹Gaubius Laboratory TNO-PG, Leiden, The Netherlands

,

Mario A. Vermeer

¹Gaubius Laboratory TNO-PG, Leiden, The Netherlands

,

Bea van der Vecht

¹Gaubius Laboratory TNO-PG, Leiden, The Netherlands

,

Victor W. M. van Hinsbergh

¹Gaubius Laboratory TNO-PG, Leiden, The Netherlands

²Institute for Cardiovascular Research, Vrije Universiteit, Amsterdam, The Netherlands

› Author Affiliations

Abstract

Summary

Among other proteolytic enzymes, the urokinase-type plasminogen activator (u-PA)/plasmin cascade contributes to cell migration and the formation of capillary-like structures in a fibrinous exudate. The u-PA receptor (u-PAR) focuses proteolytical activity on the cell surface of the endothelial cell and hereby accelerates the pericellular matrix degradation. Vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF)-2 enhance u-PA receptor expression in human endothelial cells. In this paper we show that the protein kinase C (PKC) inhibitors Ro31-8220 and GF109203X inhibit VEGF₁₆₅-induced u-PAR antigen expression in human endothelial cells, whereas PKC inhibition had no effect on FGF-2-induced u-PAR antigen enhancement. In addition, inhibition of PKC activity had no effect on VEGF_165-or FGF-2-induced proliferation in human endothelial cells. We conclude that VEGF₁₆₅ induces u-PAR via a PKC-dependent pathway, whereas proliferation is induced via a different pathway probably involving tyrosine phosphorylation of proteins downstream of the VEGF receptors.

Keywords

u-PAR - VEGF - PKC - human endothelial cells

Full Text

References

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