Potentiation of ibudilast inhibition of platelet aggregation in the presence of endothelial cells

Although communications between platelets and endothelial cells or other bl ood cells are important in in vivo thrombus formation, laboratory platelet function tests are usually performed in isolation from these surrounding ce lls. In this study, we evaluated the effect of an antiplatelet drug, ibudil ast (3-isobutyryl-2-isopropylpyrazolo[1,5-17]pyridine), on platelet aggrega tion in the presence and absence of human umbilical vein endothelial cells (HUVECs) and with the use of platelet-rich plasma (PRP) or whole blood as p latelet samples. Stimulation-dependent platelet aggregation was weakened in the presence of HUVECs, which was especially prominent when the thrombin r eceptor-activating peptide SFLL (compared with ADP and epinephrine) was use d as an aggregating agent. Ibudilast hardly affected SFLL-induced platelet aggregation (in PRP), while this antiplatelet agent was found to clearly in hibit this SELL-induced response in a concentration-dependent manner, in th e presence of HUVECs. Ibudilast tended to inhibit ADP- or epinephrine-induc ed platelet aggregation in the presence of HUVECs, but the effects were not statistically significant. Enhanced inhibition by ibudilast of SELL-induce d platelet aggregation (in the presence of HUVECs) was reproduced with the use of whole blood samples when a screen filtration pressure method was emp loyed. It is suggested that the platelet aggregation studies in the presenc e of endothelial cells and/or other blood cells provide us with valuable in formation on platelet reactivity in vivo and improvement of antiplatelet th erapy. (C) 2001 Elsevier Science I,td. All rights reserved.