Reduced thromboxane biosynthesis in carriers of toll-like receptor 4 polymorphisms in vivo
| Autor: | Maria Domenica Guglielmi, Concetta Di Febbo, Marta L. Capone, Paola Patrignani, Valeria Moretta, Stefania Tacconelli, Maria G. Sciulli, Ivana Antonucci, Ettore Porreca, Liborio Stuppia, Emanuela Ricciotti, Giovanna Baccante |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Male
Heterozygote medicine.medical_specialty Carotid Artery Common Thromboxane Immunology Prostacyclin Biochemistry Thromboxane A2 chemistry.chemical_compound Risk Factors In vivo Internal medicine medicine Humans Platelet Ultrasonography Polymorphism Genetic biology Wild type Cell Biology Hematology Middle Aged Epoprostenol Toll-Like Receptor 4 Phenotype Endocrinology Eicosanoid chemistry Cardiovascular Diseases Case-Control Studies biology.protein Female lipids (amino acids peptides and proteins) Cyclooxygenase medicine.drug |
| Zdroj: | Blood. 107:3572-3574 |
| ISSN: | 1528-0020 0006-4971 |
| DOI: | 10.1182/blood-2005-12-4811 |
| Popis: | 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 A(2) (TXA(2)) 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-TXB(2), an index of systemic biosynthesis of TX, was significantly reduced by 65%. The urinary excretion of 2,3-dinor-6-keto-prostaglandin F(1alpha), an index of systemic biosynthesis of prostacyclin, was marginally depressed but the prostacyclin/TXA(2) 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-TXB(2) 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 TXA(2) biosynthesis may contribute to the protective cardiovascular phenotype of TLR4 polymorphisms. |
| Databáze: | OpenAIRE |
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