title: Endothelial progenitor cells bind and inhibit platelet function and thrombus formation.
abstract: BACKGROUND
  Interactions of endothelial progenitor cells (EPCs) with vascular and blood cells contribute to vascular homeostasis. Although platelets promote the homing of EPCs to sites of vascular injury and their differentiation into endothelial cells, the functional consequences of such interactions on platelets remain unknown. Herein, we addressed the interactions between EPCs and platelets and their impact on platelet function and thrombus formation.
  
  
  RESULTS
  Cultured on fibronectin in conditioned media, human peripheral blood mononuclear cells differentiated, within 10 days of culture, into EPCs, which uptake acetylated low-density lipoprotein, bind ulex-lectin, lack monocyte/leukocyte markers (CD14, P-selectin glycoprotein ligand-1, L-selectin), express progenitor/endothelial markers (CD34, vascular endothelial growth factor receptor-2, von Willebrand factor, and vascular endothelial cadherin), and proliferate in culture. These EPCs bound activated platelets via CD62P and inhibited its translocation, glycoprotein IIb/IIIa activation, aggregation, and adhesion to collagen, mainly via prostacyclin secretion. Indeed, this was associated with upregulation of cyclooxygenase-2 and inducible nitric oxide synthase. However, the effects on platelets in vitro were reversed by cyclooxygenase and cyclooxygenase-2 inhibition but not by nitric oxide or inducible nitric oxide synthase inhibition. Moreover, in a ferric chloride-induced murine arterial thrombosis model, injection of EPCs led to their incorporation into sites of injury and impaired thrombus formation, leading to an incomplete occlusion with 50% residual flow.
  
  
  CONCLUSIONS
  Peripheral blood mononuclear cell-derived EPCs bind platelets via CD62P and inhibit platelet activation, aggregation, adhesion to collagen, and thrombus formation, predominantly via upregulation of cyclooxygenase-2 and secretion of prostacyclin. These findings add new insights into the biology of EPCs and define their potential roles in regulating platelet function and thrombosis.
authors.affiliation: Research Center, Montreal Heart Institute and Université de Montréal, Faculty of Medicine, Montreal, Quebec, Canada, H1T 1C8.
authors.forename: Haissam
authors.initials: H
authors.lastname: Abou-Saleh
authors.forename: Daniel
authors.initials: D
authors.lastname: Yacoub
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Théorêt
authors.forename: Marc-Antoine
authors.initials: MA
authors.lastname: Gillis
authors.forename: Paul-Eduard
authors.initials: PE
authors.lastname: Neagoe
authors.forename: Benoit
authors.initials: B
authors.lastname: Labarthe
authors.forename: Pierre
authors.initials: P
authors.lastname: Théroux
authors.forename: Martin G
authors.initials: MG
authors.lastname: Sirois
authors.forename: Maryam
authors.initials: M
authors.lastname: Tabrizian
authors.forename: Eric
authors.initials: E
authors.lastname: Thorin
authors.forename: Yahye
authors.initials: Y
authors.lastname: Merhi
mesh_terms: D001792:Blood Platelets / Q000166:cytology* / Q000502:physiology*; D020212:Carotid Artery Injuries / Q000503:physiopathology; D002478:Cells, Cultured; D011464:Epoprostenol / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D006487:Hemostasis / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology; D009569:Nitric Oxide / Q000378:metabolism; D010973:Platelet Adhesiveness / Q000502:physiology; D010974:Platelet Aggregation / Q000502:physiology; D012039:Regional Blood Flow; D013927:Thrombosis / Q000503:physiopathology*
chemical_list: D009569:Nitric Oxide; D011464:Epoprostenol