Abstract
BackgroundThe 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.MethodsEPCs 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.ResultsEPCs 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.ConclusionThis 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.
Highlights
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 observed that freshly isolated peripheral blood mononuclear cells (PBMCs) highly expressed the pan-leukocyte markers CD14 (86% ± 2%), whereas the progenitor/endothelial markers CD34 and vascular endothelial growth factor receptor 2 (VEGFR2) were missing (Figure 2)
We assessed the impact of EPCs on platelet aggregation and thrombus formation and we highlighted the role of platelet P-selectin in this process
Summary
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. Platelets favor the adhesion of EPCs onto the sub-endothelial matrix, as they constitute a bridging mechanism for the firm arrest of EPCs on collagen surfaces under dynamic flow in vitro and on the injured vessel wall in vivo [9,13]. This adhesive interaction between EPCs and platelets may improve EPC function and induce the secretion of various vasoactive substances that can modulate the microenvironment of the lesion, which in turn may enhance vascular repair and accelerate the healing process. This leads to the adhesion and activation of platelets, which is accompanied by the translocation and exposure of P-selectin (CD62P) on the membrane
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