title: Endothelial progenitor cells inhibit platelet function in a P-selectin-dependent manner.
abstract: BACKGROUND
  The role of endothelial progenitor cells (EPCs) in vascular repair is related to their recruitment at the sites of injury and their interaction with different components of the circulatory system. We have previously shown that EPCs bind and inhibit platelet function and impair thrombus formation via prostacyclin secretion, but the role of EPC binding to platelet P-selectin in this process has not been fully characterized. In the present study, we assessed the impact of EPCs on thrombus formation and we addressed the implication of P-selectin in this process.
  
  
  METHODS
  EPCs were generated from human peripheral blood mononuclear cells cultured on fibronectin in conditioned media. The impact of EPCs on platelet aggregation and thrombus formation was investigated in P-selectin deficient (P-sel(-/-)) mice and their wild-type (WT) counterparts.
  
  
  RESULTS
  EPCs significantly and dose-dependently impaired collagen-induced whole blood platelet aggregation in WT mice, whereas no effects were observed in P-sel(-/-) mice. Moreover, in a ferric chloride-induced arterial thrombosis model, infusion of EPCs significantly reduced thrombus formation in WT, but not in P-sel(-/-) mice. Furthermore, the relative mass of thrombi generated in EPC-treated P-sel(-/-) mice were significantly larger than those in EPC-treated WT mice, and the number of EPCs recruited within the thrombi and along the arterial wall was reduced in P-sel(-/-) mice as compared to WT mice.
  
  
  CONCLUSIONS
  This study shows that EPCs impair platelet aggregation and reduce thrombus formation via a cellular mechanism involving binding to platelet P-selectin. These findings add new insights into the role of EPC-platelet interactions in the regulation of thrombotic events during vascular repair.
authors.affiliation: Qatar Cardiovascular Research Center, Qatar Foundation, Education City, Doha, Qatar. hasaleh@qf.org.qa.
authors.forename: Haissam
authors.initials: H
authors.lastname: Abou-Saleh
authors.affiliation: Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, 5000 Belanger, Montreal, H1T 1C8, QC, Canada. ahmed_hachem@hotmail.com.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Hachem
authors.affiliation: Laboratoire d'Immunologie Cellulaire et Moléculaire, Centre de recherche du Centre Hospitalier de l'Université de Montréal, Montreal, QC, Canada. yacoub.dy@gmail.com.
authors.forename: Daniel
authors.initials: D
authors.lastname: Yacoub
authors.affiliation: Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, 5000 Belanger, Montreal, H1T 1C8, QC, Canada. marc-antoine.gillis@icm-mhi.org.
authors.forename: Marc-Antoine
authors.initials: MA
authors.lastname: Gillis
authors.affiliation: Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, 5000 Belanger, Montreal, H1T 1C8, QC, Canada. yahye.merhi@icm-mhi.org.|Faculty of Medicine, Université de Montréal, Montreal, QC, Canada. yahye.merhi@icm-mhi.org.
authors.forename: Yahye
authors.initials: Y
authors.lastname: Merhi
mesh_terms: D000328:Adult; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D002339:Carotid Arteries / Q000473:pathology; D066026:Endothelial Progenitor Cells / Q000166:cytology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D008875:Middle Aged; D019007:P-Selectin / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D010974:Platelet Aggregation; D011485:Protein Binding; D013927:Thrombosis / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D019007:P-Selectin; C546937:SELP protein, human