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(Circulation. 2009;120:2230-2239.)
© 2009 American Heart Association, Inc.

Molecular Cardiology

Endothelial Progenitor Cells Bind and Inhibit Platelet Function and Thrombus Formation

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

From the Research Center, Montreal Heart Institute and Université de Montréal, Faculty of Medicine (H.A.-S., D.Y., J.T., M.G., P.N., B.L., P.T., M.G.S., E.T., Y.M.); and McGill University (M.T.), Montreal, Quebec, Canada.

Correspondence to Yahye Merhi, PhD, Laboratory of Thrombosis and Hemostasis, Montreal Heart Institute, 5000 Belanger, Montreal, Quebec, Canada, H1T 1C8. E-mail yahye.merhi{at}icm-mhi.org

Received January 14, 2009; accepted September 23, 2009.

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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CLINICAL PERSPECTIVE

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Clinical Summaries
Circulation 2009 120: 2163-2165. [Extract] [Full Text]