Endothelial progenitor cells bind and inhibit platelet function and thrombus formation

Haissam Abou-Saleh, Daniel Yacoub, Jean François Théorêt, Marc Antoine Gillis, Paul Eduard Neagoe, Benoit Labarthe, Pierre Théroux, Martin G. Sirois, Maryam Tabrizian, Eric Thorin, Yahye Merhi

Research output: Contribution to journalArticle

59 Citations (Scopus)

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. METHODS AND 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.

Original languageEnglish
Pages (from-to)2230-2239
Number of pages10
JournalCirculation
Volume120
Issue number22
DOIs
Publication statusPublished - Dec 2009
Externally publishedYes

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Thrombosis
Blood Platelets
Cyclooxygenase 2
Blood Cells
Nitric Oxide Synthase Type II
Epoprostenol
Blood Vessels
Up-Regulation
Collagen
L-Selectin
Vascular Endothelial Growth Factor Receptor-2
Platelet Glycoprotein GPIIb-IIIa Complex
Endothelial Progenitor Cells
Vascular System Injuries
Platelet Activation
von Willebrand Factor
Prostaglandin-Endoperoxide Synthases
Conditioned Culture Medium
Platelet Aggregation
Fibronectins

Keywords

  • Nitric oxide
  • Platelets
  • Progenitor cells
  • Prostaglandins
  • Thrombosis

ASJC Scopus subject areas

  • Physiology (medical)
  • Cardiology and Cardiovascular Medicine

Cite this

Abou-Saleh, H., Yacoub, D., Théorêt, J. F., Gillis, M. A., Neagoe, P. E., Labarthe, B., ... Merhi, Y. (2009). Endothelial progenitor cells bind and inhibit platelet function and thrombus formation. Circulation, 120(22), 2230-2239. https://doi.org/10.1161/CIRCULATIONAHA.109.894642

Endothelial progenitor cells bind and inhibit platelet function and thrombus formation. / Abou-Saleh, Haissam; Yacoub, Daniel; Théorêt, Jean François; Gillis, Marc Antoine; Neagoe, Paul Eduard; Labarthe, Benoit; Théroux, Pierre; Sirois, Martin G.; Tabrizian, Maryam; Thorin, Eric; Merhi, Yahye.

In: Circulation, Vol. 120, No. 22, 12.2009, p. 2230-2239.

Research output: Contribution to journalArticle

Abou-Saleh, H, Yacoub, D, Théorêt, JF, Gillis, MA, Neagoe, PE, Labarthe, B, Théroux, P, Sirois, MG, Tabrizian, M, Thorin, E & Merhi, Y 2009, 'Endothelial progenitor cells bind and inhibit platelet function and thrombus formation', Circulation, vol. 120, no. 22, pp. 2230-2239. https://doi.org/10.1161/CIRCULATIONAHA.109.894642
Abou-Saleh H, Yacoub D, Théorêt JF, Gillis MA, Neagoe PE, Labarthe B et al. Endothelial progenitor cells bind and inhibit platelet function and thrombus formation. Circulation. 2009 Dec;120(22):2230-2239. https://doi.org/10.1161/CIRCULATIONAHA.109.894642
Abou-Saleh, Haissam ; Yacoub, Daniel ; Théorêt, Jean François ; Gillis, Marc Antoine ; Neagoe, Paul Eduard ; Labarthe, Benoit ; Théroux, Pierre ; Sirois, Martin G. ; Tabrizian, Maryam ; Thorin, Eric ; Merhi, Yahye. / Endothelial progenitor cells bind and inhibit platelet function and thrombus formation. In: Circulation. 2009 ; Vol. 120, No. 22. pp. 2230-2239.
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AU - Abou-Saleh, Haissam

AU - Yacoub, Daniel

AU - Théorêt, Jean François

AU - Gillis, Marc Antoine

AU - Neagoe, Paul Eduard

AU - Labarthe, Benoit

AU - Théroux, Pierre

AU - Sirois, Martin G.

AU - Tabrizian, Maryam

AU - Thorin, Eric

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N2 - 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. METHODS AND 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.

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KW - Nitric oxide

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KW - Progenitor cells

KW - Prostaglandins

KW - Thrombosis

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