Abstract 377: Soluble CD40 Ligand Reverses the Inhibitory Effect of Early Endothelial Progenitor Cells on Platelet Aggregation

Abstract

Introduction and hypothesis: Circulating Endothelial progenitor cells (EPCs) interact with other blood cells and platelets and may contribute to limit the thrombo-inflammatory reactions at the sites of vascular injury. Indeed, we have previously shown that EPCs inhibit platelet activation and aggregation. The CD40/CD40L axis is a thrombo-inflammatory mediator that affects platelet and endothelial functions. EPCs express CD40 while platelets represent the major source of soluble CD40 ligand (sCD40L) in the circulation. We aimed to demonstrate the existence of a sCD40L/CD40 signaling pathway in EPCs and to test the hypothesis that sCD40L affects the anti-platelet function of EPCs. Methods and results: Human peripheral blood mononuclear cell-derived early EPCs in culture express CD40 and its adaptor proteins, the tumor necrosis factor associated factors: TRAF1, TRAF2 and TRAF3. sCD40L stimulation of early EPCs had no effect on TRAF2 expression, but increased its binding to CD40. In contrast, sCD40L increased the expression of TRAF1 and affected its binding to CD40; whereas TRAF3 binding was not affected. In functional studies, pretreatment of early EPCs with sCD40L had no effect on their viability, but reduced their inhibitory effect on platelet aggregation. However, the release of the anti-aggregating agents prostacyclin and nitric oxide by early EPCs was not affected by sCD40L treatment. Conclusion: We have revealed the existence of the CD40L/CD40/TRAF axis in early EPCs, which reduced their anti-platelet properties. This was not related to an effect of sCD40L on early EPC survival nor on their release of prostacyclin or nitric oxide.