title: Potentiation of ibudilast inhibition of platelet aggregation in the presence of endothelial cells.
abstract: Although communications between platelets and endothelial cells or other blood cells are important in in vivo thrombus formation, laboratory platelet function tests are usually performed in isolation from these surrounding cells. In this study, we evaluated the effect of an antiplatelet drug, ibudilast (3-isobutyryl-2-isopropylpyrazolo[1,5-a]pyridine), on platelet aggregation 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 platelet samples. Stimulation-dependent platelet aggregation was weakened in the presence of HUVECs, which was especially prominent when the thrombin receptor-activating peptide SFLL (compared with ADP and epinephrine) was used as an aggregating agent. Ibudilast hardly affected SFLL-induced platelet aggregation (in PRP), while this antiplatelet agent was found to clearly inhibit this SFLL-induced response in a concentration-dependent manner, in the presence of HUVECs. Ibudilast tended to inhibit ADP- or epinephrine-induced platelet aggregation in the presence of HUVECs, but the effects were not statistically significant. Enhanced inhibition by ibudilast of SFLL-induced platelet aggregation (in the presence of HUVECs) was reproduced with the use of whole blood samples when a screen filtration pressure method was employed. It is suggested that the platelet aggregation studies in the presence of endothelial cells and/or other blood cells provide us with valuable information on platelet reactivity in vivo and improvement of antiplatelet therapy.
authors.affiliation: Department of Clinical and Laboratory Medicine, Yamanashi Medical University, Tamaho, Yamanashi 409-3898, Nakakoma, Japan.
authors.forename: G
authors.initials: G
authors.lastname: Rile
authors.forename: Y
authors.initials: Y
authors.lastname: Yatomi
authors.forename: R
authors.initials: R
authors.lastname: Qi
authors.forename: K
authors.initials: K
authors.lastname: Satoh
authors.forename: Y
authors.initials: Y
authors.lastname: Ozaki
mesh_terms: D001792:Blood Platelets / Q000166:cytology; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D007700:Kinetics; D010446:Peptide Fragments / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D014471:Umbilical Veins / Q000737:chemistry / Q000166:cytology; D007212:Indolizines; D011720:Pyrazoles
chemical_list: D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; C072032:thrombin receptor peptide (42-55); C038366:ibudilast; D007212:Indolizines; D011720:Pyrazoles