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. Key Words: progenitor cells Ⅲ nitric oxide Ⅲ platelets Ⅲ prostaglandins Ⅲ thrombosis E ndothelial progenitor cells (EPCs) are believed to contribute to vascular biology and hemostasis. Although EPCs have been localized in cord blood, bone marrow, and peripheral blood as well as in some regenerative tissues, controversy relative to their isolation, identification, and functionality still exists. Indeed, the term EPC has been employed to describe different populations of multipotent cells that have the capability to differentiate, depending on the environmental cues, into mature endothelial cells (ECs). These cells are extremely rare in peripheral blood, but their number can be markedly increased after treatment with mobilizing cytokines or vascular trauma. 1 Nevertheless, cells with progenitor and endothelial phenotypes have been generated in vitro from peripheral blood mononuclear cells (PBMCs) 2-10 and have shown potential therapeutic applications in vascular tissue engineering and cell-based therapy. 5...
The evaluation of clopidogrel responsiveness by platelet function tests is largely influenced by the choice of blood preservative and functional tests. Measures of aggregation stabilization, and of consequent secretion and activation, identified most patients as responders, contrasting with measures of peak aggregation, by likely reflecting better the interactions clopidogrel and the P2Y12 receptor.
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