Evaluation of the antiplatelet effects of cilostazol, a phosphodiesterase 3 inhibitor, by VASP phosphorylation and platelet aggregation.
Evaluation of the antiplatelet effects of cilostazol, a phosphodiesterase 3 inhibitor, by VASP phosphorylation and platelet aggregation.
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DOI：
10.1253/circj.cj-08-0289
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发表时间：
2008-10
期刊：
影响因子：
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通讯作者：
Hiromi Yamamoto;Kanako Takahashi;Haruyo Watanabe;Yuka Yoshikawa;R. Shirakawa;T. Higashi;Mitsunori Kawato;Tomoyuki Ikeda;A. Tabuchi;T. Morimoto;T. Kita;H. Horiuchi
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文献类型：
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作者：
Hiromi Yamamoto;Kanako Takahashi;Haruyo Watanabe;Yuka Yoshikawa;R. Shirakawa;T. Higashi;Mitsunori Kawato;Tomoyuki Ikeda;A. Tabuchi;T. Morimoto;T. Kita;H. Horiuchi
背景西洛他唑是一种磷酸二酯酶3抑制剂，是一种广泛用于预防心血管事件的抗血小板药物，尽管迄今为止，评估其效果的方法很少。方法和结果 在 10 名健康男性受试者摄入 100 mg 西洛他唑后，在基线以及 3 小时和 12 小时采集血样。在 8 nmol/L 前列腺素 E(1) (PGE(1)) 处理之前和之后，通过蛋白质印迹检查血管舒张刺激磷蛋白 (VASP)（血小板中丰富的 cAMP 依赖性激酶底物）的磷酸化水平，并通过光学聚集计检查 ADP 和胶原诱导的聚集。西洛他唑摄入量不会影响 VASP 磷酸化水平或未经 PGE(1) 治疗的最大聚集率。然而，西洛他唑的摄入明显增强了PGE(1)诱导的VASP磷酸化以及PGE(1)介导的ADP和胶原诱导的最大聚集率的降低。 Ser157 磷酸化的 VASP 水平相关，ADP 诱导的最大聚集率与血浆中西洛他唑浓度呈负相关。结论 摄入西洛他唑的抗血小板作用可以通过测量低浓度 PGE 离体处理后血小板中 VASP 磷酸化水平和最大聚集率来评估 (1)。
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).