The angiopoietin pathway is modulated by PAR-1 activation on human endothelial progenitor cells.
OBJECTIVE
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.


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.
Smadja
D M
DM
Université Paris-Descartes, INSERM Unité 765, Hôpital Européen Georges Pompidou, Paris, France.
Laurendeau
I
I
Avignon
C
C
Vidaud
M
M
Aiach
M
M
Gaussem
P
P
D042683:Angiopoietin-1 / Q000378:metabolism* / Q000502:physiology; D042702:Angiopoietin-2 / Q000502:physiology*; D018952:Antigens, CD34; D002454:Cell Differentiation; D002465:Cell Movement; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D005312:Fetal Blood / Q000166:cytology; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D018919:Neovascularization, Physiologic; D010446:Peptide Fragments / Q000494:pharmacology; D044463:Receptor, PAR-1 / Q000235:genetics / Q000378:metabolism*
D042683:Angiopoietin-1; D042702:Angiopoietin-2; D018952:Antigens, CD34; D010446:Peptide Fragments; D044463:Receptor, PAR-1; C082835:thrombin receptor peptide (42-47)