Evaluation of the Antiplatelet Effects of Cilostazol, a Phosphodiesterase 3 Inhibitor, by VASP Phosphorylation and Platelet Aggregation

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Background Cilostazol, a phosphodiesterase 3 inhibitor, is an antiplatelet drug that is widely used for preventing cardiovascular events, although, to date, there are few methods for evaluating its effects. Methods and Results Blood samples were taken at baseline and at 3 and 12h in 10 healthy male subjects after 100mg cilostazol intake. Each sample was examined by Western blot for phosphorylation levels of vasodilator-stimulated phosphoprotein (VASP), an abundant cAMP-dependent kinase substrate in platelets, and by the optical aggregometer for ADP- and collagen-induced aggregation, before and after 8 nmol/L prostaglandin E_1 (PGE_1) treatment. Cilostazol intake did not affect VASP phosphorylation levels or the maximal aggregation rates without PGE_1 treatment. However, cilostazol intake apparently enhanced PGE_1-induced VASP phosphorylation and PGE_1-mediated reduction of ADP-and collagen-induced maximal aggregation rates. Levels of VASP phosphorylated at Ser157 were correlated and the maximal aggregation rates induced by ADP were inversely correlated with cilostazol concentrations in the plasma. Conclusion The antiplatelet effects of cilostazol intake could be evaluated by measuring VASP phosphorylation levels and maximal aggregation rates in platelets by ex vivo treatment with a low concentration of PGE_1.
社団法人日本循環器学会の論文
2008-10-20