title: PAR-1 activation on human late endothelial progenitor cells enhances angiogenesis in vitro with upregulation of the SDF-1/CXCR4 system.
abstract: OBJECTIVE
  The importance of PAR-1 in blood vessel development has been demonstrated in knockout mice. As endothelial progenitor cells (EPCs) are involved in postnatal vasculogenesis, we examined whether they express PAR-1 and whether stimulation by the peptide SFLLRN modulates their angiogenic properties.
  
  
  RESULTS
  EPC expanded from human CD34+ cord blood cells expressed PAR-1. PAR-1 activation induced EPC proliferation in a concentration-dependent manner far more potently than that of human umbilical vein endothelial cells. PAR-1 activation also enhanced actin reorganization, promoting both spontaneous migration in a Boyden chamber assay and migration toward SDF-1 and VEGF. As shown by real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR), EPC stimulation by SFLLRN significantly enhanced the mRNA expression of SDF-1 and its receptor CXCR-4. PAR-1 activation also increased CXCR4 expression on EPC and induced SDF-1 secretion, leading to autocrine stimulation. PAR-1 stimulation by SFLLRN also increased the formation of capillary-like structures by EPC in Matrigel, and this effect was abrogated by anti-CXCR-4, anti-SDF-1, and MEK inhibitor pretreatment.
  
  
  CONCLUSIONS
  Human EPCs express functional PAR-1. PAR-1 activation promotes cell proliferation and CXCR4-dependent migration and differentiation, leading to a proangiogenic effect.
authors.affiliation: INSERM Unité 428, Hôpital Européen Georges Pompidou (AP-HP), Université Paris V, Paris, France.
authors.forename: David M
authors.initials: DM
authors.lastname: Smadja
authors.forename: Ivan
authors.initials: I
authors.lastname: Bièche
authors.forename: Georges
authors.initials: G
authors.lastname: Uzan
authors.forename: Heidi
authors.initials: H
authors.lastname: Bompais
authors.forename: Laurent
authors.initials: L
authors.lastname: Muller
authors.forename: Catherine
authors.initials: C
authors.lastname: Boisson-Vidal
authors.forename: Michel
authors.initials: M
authors.lastname: Vidaud
authors.forename: Martine
authors.initials: M
authors.lastname: Aiach
authors.forename: Pascale
authors.initials: P
authors.lastname: Gaussem
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000906:Antibodies / Q000494:pharmacology; D018952:Antigens, CD34 / Q000378:metabolism; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics; D042783:Endothelial Cells / Q000166:cytology* / Q000502:physiology; D005312:Fetal Blood / Q000166:cytology; D015870:Gene Expression / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D018919:Neovascularization, Physiologic / Q000502:physiology*; D044463:Receptor, PAR-1 / Q000235:genetics / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D000906:Antibodies; D018952:Antigens, CD34; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D016207:Cytokines; D044463:Receptor, PAR-1; D019718:Receptors, CXCR4