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Blood, 1 May 2006, Vol. 107, No. 9, pp. 3572-3574. Prepublished online as a Blood First Edition Paper on January 5, 2006; DOI 10.1182/blood-2005-12-4811. This Article Full Text (PDF) All Versions of this Article: 2005-12-4811v1 107/9/3572    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Patrignani, P. Articles by Porreca, E. Search for Related Content PubMed PubMed Citation Articles by Patrignani, P. Articles by Porreca, E. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 6, 2005 Accepted December 24, 2005 Reduced thromboxane biosynthesis in carriers of toll-like receptor 4 polymorphisms in vivo Paola Patrignani*, Concetta Di Febbo, Stefania Tacconelli, Valeria Moretta, Giovanna Baccante, Maria G Sciulli, Emanuela Ricciotti, Marta L Capone, Ivana Antonucci, Maria D Guglielmi, Liborio Stuppia, and Ettore Porreca Departments of Medicine and Aging, G dAnnunzio University, Chieti, Italy Biomedical Sciences, "G. d'Annunzio" University and "Gabriele d'Annunzio" University Foundation, Chieti, Italy * Corresponding author; email: ppatrignani{at}unich.it. The recent demonstration that platelets express a functional toll-like receptor 4(TLR4) prompted us to explore the influence of TLR4 polymorphisms(Asp299Gly alone or in combination with Thr399Ile) on thromboxane(TX)A2 biosynthesis in vivo. In 17 subjects with TLR4 polymorphisms versus 17 wild-type (untreated with aspirin, matched for age, sex and cardiovascular risk factors) intima/media thickness in the common carotid arteries was significantly lower. Average urinary excretion of 11-dehydro-TXB2, an index of systemic biosynthesis of TX, was significantly reduced by 65%. The urinary excretion of 2,3-dinor-6-keto-prostaglandin F1, an index of systemic biosynthesis of prostacyclin, was marginally depressed but prostacyclin/TXA2 biosynthesis ratio was significantly higher than in wild-type. Selective inhibition of cyclooxygenase-2-dependent prostacyclin(by rofecoxib or etoricoxib) was associated with increased urinary excretion of 11-dehydro-TXB2 in carriers of TLR4 polymorphisms, but not in wild-type, suggesting a restrainable effect of prostacyclin on platelet function in vivo in this setting. Reduced TXA2 biosynthesis may contribute to the protective cardiovascular phenotype of TLR4 polymorphisms. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. Blair, S. Rex, O. Vitseva, L. Beaulieu, K. Tanriverdi, S. Chakrabarti, C. Hayashi, C. A. Genco, M. Iafrati, and J. E. Freedman Stimulation of Toll-Like Receptor 2 in Human Platelets Induces a Thromboinflammatory Response Through Activation of Phosphoinositide 3-Kinase Circ. Res., February 13, 2009; 104(3): 346 - 354. [Abstract] [Full Text] [PDF]

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