Evaluation of the antiplatelet effects of cilostazol, a phosphodiesterase 3 inhibitor, by VASP phosphorylation and platelet aggregation.

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 12 h in 10 healthy male subjects after 100 mg 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).