Clopidogrel increases expression of chemokines in peripheral blood mononuclear cells in patients with coronary artery disease: results of a double‐blind placebo‐controlled study
| Autor: | Erik Gjertsen, P. Aukrust, Stig S. Frøland, V. Hansteen, Nils Olav Solum, A.K. Andreassen, Turid M. Pedersen, Thor Ueland, Anne Grete Semb, Torgun Wæhre, Frank Brosstad, Lars Gullestad, A. Yndestad, Jan Kristian Damås |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Chemokine Ticlopidine Coronary Artery Disease Peripheral blood mononuclear cell Immunoenzyme Techniques Placebos Chemokine receptor Double-Blind Method Humans Medicine Platelet cardiovascular diseases Platelet activation Cells Cultured Aged biology Reverse Transcriptase Polymerase Chain Reaction business.industry Hematology Middle Aged Clopidogrel Gene Expression Regulation Immunology Leukocytes Mononuclear biology.protein Platelet aggregation inhibitor Female Endothelium Vascular Chemokines business Platelet Aggregation Inhibitors medicine.drug |
| Zdroj: | Journal of Thrombosis and Haemostasis. 4:2140-2147 |
| ISSN: | 1538-7836 |
| DOI: | 10.1111/j.1538-7836.2006.02131.x |
| Popis: | Background Chemokines and platelet activation are both important in atherogenesis. Platelet inhibitors are widely used in coronary artery disease (CAD), and we hypothesized that the platelet inhibitor clopidogrel could modify chemokines in CAD patients. Objectives We sought to investigate the effect of clopidogrel on the expression of chemokines and chemokine receptors in peripheral blood mononuclear cells (PBMC) in CAD patients. Patients/methods Thirty-seven patients with stable angina were randomized to clopidogrel (n = 18) or placebo (n = 19). PBMC, blood platelets and plasma were collected at baseline and after 7-10 days in the patients, and in 10 healthy controls. mRNA levels of chemokines and chemokine receptors in PBMC were analyzed by ribonuclease protection assays and real-time reverse transcriptase polymerase chain reaction. Platelet activation was studied by flow cytometry. Results (i) At baseline, the gene expression of the regulated on activation normally T-cell expressed and secreted (RANTES) chemokines and macrophage inflammatory peptide (MIP)-1beta in PBMC, the expression of CD62P and CD63 on platelets and the levels of platelet-derived microparticles (PMP) were elevated in angina patients comparing healthy controls; (ii) markers of platelet activation were either reduced (CD63) or unchanged (CD62P, PMP, beta-thromboglobulin) during clopidogrel therapy; (iii) in contrast, clopidogrel significantly up-regulated the gene expression of RANTES and MIP-1beta in PBMC, while no changes were found in the placebo group; (iv) a stable adenosine 5'-diphosphate metabolite attenuated the release of MIP-1beta, but not of RANTES, from activated PBMC in vitro. Conclusions Even if we do not argue against a beneficial role for clopidogrel in CAD, our findings may suggest potential inflammatory effects of clopidogrel in CAD. |
| Databáze: | OpenAIRE |
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