Platelet responsiveness to in vitro aspirin is independent of COX-1 and COX-2 protein levels and polymorphisms.

Platelet responsiveness to in vitro aspirin is independent of COX-1 and COX-2 protein levels and polymorphisms. Research Abstract Details 

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Platelet responsiveness to in vitro aspirin is independent of COX-1 and COX-2 protein levels and polymorphisms. Abstract Text:

Shinichi Takahashi,Miho Ushida,Risa Komine,Aya Shimodaira,Toshihiro Uchida,Hiroaki Ishihara,Toshiro Shibano,Gentaro Watanabe,Yasuo Ikeda,Mitsuru Murata,

Aspirin's inhibitory effect on platelet function has been shown to be highly heterogeneous. However, due to the considerable individual variation in pharmacokinetics after aspirin intake, it has been difficult to investigate the mechanism of aspirin resistance empirically. Our objective was to examine whether platelet responsiveness to in vitro aspirin treatment could be affected by cyclooxygenase (COX)-1/2 protein levels in platelets or single-nucleotide polymorphisms (SNPs), which could possibly change specific activity of enzymes and/or aspirin susceptibility. Collagen/epinephrine closure time (CEPI-CT) of PFA-100 in blood from 178 healthy males was assessed with/without aspirin. Platelet COX-1 protein levels and the sequences of COX-1 gene exons were examined in three groups categorized by CEPI-CT: PR (Poor responders to aspirin), 10 people showing the shortest CEPI-CT under aspirin; GR-High or GR-Low (good responders to aspirin with high or low platelet basal reactivity), 10 people showing CEPI-CT over 300 s under aspirin and having the shortest or longest basal CEPI-CT, respectively. We analyzed the three groups, representing phenotypic extremes, aiming to increase statistical power to investigate the possible relevance of COXs to platelet response to aspirin. Western blot analysis revealed that COX-1 was abundantly expressed in platelets at comparable levels among the three groups, whereas COX-2 was undetectable. The frequencies of nonsynonymous COX-1/2 SNPs were unlikely to explain the difference in aspirin responsiveness considering the observed genotype frequencies and wide individual variation in platelet response. These results suggest that heterogeneity in platelet responsiveness to in vitro aspirin is independent of COX-1/2 protein levels and SNPs.

Platelet responsiveness to in vitro aspirin is independent of COX-1 and COX-2 protein levels and polymorphisms. Publishing Authors By Initials

S Takahashi,M Ushida,R Komine,A Shimodaira,T Uchida,H Ishihara,T Shibano,G Watanabe,Y Ikeda,M Murata,

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Platelet responsiveness to in vitro aspirin is independent of COX-1 and COX-2 protein levels and polymorphisms. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Thrombosis research

VOLUME: 121

Page Numbers: 509-17

Journal Abbreviation: Thromb. Res.

ISSN: 0049-3848

DAY: 13

MONTH: 07

YEAR: 2007

Platelet responsiveness to in vitro aspirin is independent of COX-1 and COX-2 protein levels and polymorphisms. Information

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LANGUAGE: eng

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Grant and Affiliation Information for Platelet responsiveness to in vitro aspirin is independent of COX-1 and COX-2 protein levels and polymorphisms.

AFFILIATION: The Keio-Daiichi Project on Genetics of Thrombosis, Keio University, Tokyo 160-8582, Japan; Biological Research Laboratories I, DAIICHI SANKYO Co., Ltd., Tokyo 134-8630, Japan.

Country: United States

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MEDLINETA: Thromb Res

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