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...

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Published in:Circulation Journal 2008, Vol.72(11), pp.1844-1851
Main Authors: Yamamoto, Hiromi, Takahashi, Kanako, Watanabe, Haruyo, Yoshikawa, Yuka, Shirakawa, Ryutaro, Higashi, Tomohito, Kawato, Mitsunori, Ikeda, Tomoyuki, Tabuchi, Arata, Morimoto, Takeshi, Kita, Toru, Horiuchi, Hisanori
Format: Article
Language:English
Subjects:
Adult
Alprostadil - pharmacology
Antiplatelet
Blood Platelets - metabolism
Cell Adhesion Molecules - metabolism
Cilostazol
Humans
Male
Microfilament Proteins - metabolism
Middle Aged
Phosphodiesterase 3 Inhibitors
Phosphoproteins - metabolism
Phosphorylation - drug effects
Platelet Aggregation - drug effects
Platelet Aggregation Inhibitors - administration & dosage
Platelets
Prostaglandins
Signal transduction
Tetrazoles - administration & dosage
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Summary: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 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 PGE1-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. (Circ J 2008; 72: 1844 - 1851)
ISSN:1346-9843
1347-4820
DOI:10.1253/circj.CJ-08-0289