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The Angiopoietin Pathway Is Modulated by PAR-1 Activation on Human Endothelial Progenitor Cells

The Angiopoietin Pathway Is Modulated by PAR-1 Activation on Human Endothelial Progenitor Cells

D M Smadja, I Laurendeau, C Avignon, M Vidaud, M Aiach, P Gaussem

J Thromb Haemost. 2006 Sep;4(9):2051-8.

PMID: 16803467

Abstract:

Objectives:
The importance of protease-activated receptor-1 (PAR-1) in blood vessel development has been shown in knock-out mice. As endothelial progenitor cells (EPCs) express functional PAR-1, we examined whether PAR-1 stimulation by the peptide SFLLRN interfered with the angiopoietin pathway, that is EPC commitment, proliferation and migration.
Methods and results:
Given the strong PAR-1 expression on CD34+ cells, we tested the effect of SFLLRN 75 micromol L(-1) on the emergence of EPCs from cord blood. PAR-1 activation did not modify the number of colonies or the day of emergence, in keeping with the lack of induction of angiopoietin 1 gene expression. Conversely, SFLLRN treatment of EPCs induced angiopoietin 2 gene expression and protein synthesis. Experiments with polyclonal blocking antibodies showed that angiopoietin 2 was involved in the proliferative effect of PAR-1 activation. PAR-1 activation also enhanced migration toward angiopoietin 1 in a Boyden chamber assay.
Conclusions:
Our study demonstrates that PAR-1-induced proliferation of EPCs involves angiopoietin 2. PAR-1 also enhances EPC migration toward angiopoietin 1. These findings might explain the role of thrombin in neovascularization via the angiopoietin pathway.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4248741	Angiopoietin-1 human			Price

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