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The angiopoietin pathway is modulated by PAR‐1 activation on human endothelial progenitor cells
Author(s) -
SMADJA D. M.,
LAURENDEAU I.,
AVIG C.,
VIDAUD M.,
AIACH M.,
GAUSSEM P.
Publication year - 2006
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2006.02101.x
Subject(s) - angiopoietin 2 , angiopoietin , progenitor cell , microbiology and biotechnology , progenitor , endothelial progenitor cell , chemistry , cancer research , biology , stem cell , vegf receptors , vascular endothelial growth factor
Summary. 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 μ mol 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.