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

Hiromi Yamamoto, Kanako Takahashi, Haruyo Watanabe, Yuka Yoshikawa, Ryutaro Shirakawa, Tomohito Higashi, Mitsunori Kawato, Tomoyuki Ikeda, Arata Tabuchi, Takeshi Morimoto, Toru Kita, Hisanori Horiuchi

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

Abstract

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 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 E1 (PGE1) treatment. Cilostazol intake did not affect VASP phosphorylation levels or the maximal aggregation rates without PGE1 treatment. However, cilostazol intake apparently enhanced PGE1-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 PGE1.

Original languageEnglish
Pages (from-to)1844-1851
Number of pages8
JournalCirculation Journal
Volume72
Issue number11
DOIs
Publication statusPublished - 2008
Externally publishedYes

Keywords

  • Antiplatelet
  • Cilostazol
  • Platelets
  • Prostaglandins
  • Signal transduction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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