title: Soluble CD40 ligand impairs the anti-platelet function of peripheral blood angiogenic outgrowth cells via increased production of reactive oxygen species.
abstract: Adult peripheral blood angiogenic early outgrowth cells (EOCs), also known as early endothelial progenitor cells, interact with other blood and vascular cells and may regulate atherothrombosis. We have previously shown that endothelial progenitor cells inhibit platelet function and thrombus formation. The CD40L/CD40 axis is a thrombo- inflammatory mediator that affects platelet and endothelial functions. It has been shown that EOCs express CD40, whereas platelets represent the major source of its soluble ligand (sCD40L), which impairs EOC function.We aimed to test the hypothesis that the sCD40L/CD40 axis affects the anti-platelet function of EOCs. Human peripheral blood mononuclear cell-derived EOCs in culture inhibited platelet aggregation. Pre-treatment of EOCs with sCD40L reduced their inhibitory effect on platelet aggregation in a CD40-dependent manner. EOCs viability and release of the anti-aggregating agents, prostacyclin and nitric oxide, were not affected by sCD40L. However, production of reactive oxygen species (ROS) was increased in sCD40L-treated EOCs. Blockade of ROS reversed the effects of sCD40L-treated EOCs on platelet aggregation. This study reveals that the sCD40L/CD40 axis impairs the anti-platelet properties of EOCs through increased production of ROS. These data may explain the link between elevated levels of sCD40L, impaired activity of EOCs and enhanced platelet reactivity, and consequently the occurrence of atherothrombotic disease.
authors: Laboratory of Thrombosis and Haemostasis, Montreal Heart Institute, 5000 Belanger, Montréal, Québec, Canada.
authors: L
authors: L
authors: Bou Khzam
authors: A
authors: A
authors: Hachem
authors: Y
authors: Y
authors: Zaid
authors: R
authors: R
authors: Boulahya
authors: W
authors: W
authors: Mourad
authors: Y
authors: Y
authors: Merhi
mesh_terms: D017209:Apoptosis; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism*; D002470:Cell Survival; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D010974:Platelet Aggregation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
chemical_list: D019013:CD40 Antigens; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D023201:CD40 Ligand; D009569:Nitric Oxide; D011464:Epoprostenol