Cilostazol exerted stronger antiplatelet effects than aspirin by significantly suppressing thrombin-stimulated increases in intracellular Ca2+ and platelet aggregation, although both drugs' effects were attenuated in thrombin-activated platelets.
Do aspirin and cilostazol reduce intracellular Ca2+ mobilization and aggregation in thrombin-activated human platelets?
In a human platelet model, cilostazol demonstrated stronger antiplatelet effects than aspirin, and both agents showed attenuated efficacy in thrombin-activated platelets, highlighting the potential of this model for studying arterial occlusive disease.
Platelets play an important role in physiological hemostatic mechanisms. In contrast, platelet activation has been implicated in pathological conditions, such as atherosclerosis, angiogenesis, and inflammation. Thrombin is considered to be of particular pathological importance as a platelet-activating substance, and thrombin-activated platelets are detected in the blood of patients with advanced occlusive arterial disease. Ca2+ acts as a second messenger in platelet activation, and the regulation of intracellular Ca2+ concentrations (Ca2+i) is important for controlling platelet functions. However, changes in Ca2+i by antiplatelet agents remain unclear. Therefore, we herein investigated the relationship between Ca2+i and the intensity of platelet aggregation after a thrombin stimulation, the relationship between Ca2+i and the intensity of platelet aggregation by antiplatelet agents, and the effects of antiplatelet agents on thrombin-activated platelets as a surrogate platelet model for arterial occlusive disease. Fura2-loaded platelets were treated with phosphate-buffered saline or a low concentration of thrombin (0.005 U/mL), followed by antiplatelet agents (aspirin or cilostazol), and changes in Ca2+i and the intensity of platelet aggregation by the thrombin stimulation were measured using fluorescence spectrophotometry. Changes in Ca2+i and the intensity of platelet aggregation after the thrombin stimulation as well as the relationship between Ca2+i and the intensity of platelet aggregation by antiplatelet agents indicated that cilostazol exerted stronger antiplatelet effects than aspirin and also that antiplatelet effects may be attenuated in thrombin-activated platelets. The present results also suggest the utility of thrombin-activated platelets as a surrogate platelet model for arterial occlusive disease. These results may contribute to future drug development for antiplatelet therapy. J. Med. Invest. 70 : 94-100, February, 2023
Sone et al. (Sun,) conducted a other in Healthy volunteers (platelet donor model) (n=6). Aspirin and Cilostazol vs. Control (vehicle) was evaluated on Intracellular Ca2+ mobilization and intensity of platelet aggregation. Cilostazol exerted stronger antiplatelet effects than aspirin by significantly suppressing thrombin-stimulated increases in intracellular Ca2+ and platelet aggregation, although both drugs' effects were attenuated in thrombin-activated platelets.
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