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Clopidogrel increases expression of chemokines in peripheral blood mononuclear cells in patients with coronary artery disease: results of a double‐blind placebo‐controlled study
Author(s) -
WÆHRE T.,
DAMÅS J. K.,
PEDERSEN T. M.,
GULLESTAD L.,
YNDESTAD A.,
ANDREASSEN A. K.,
FRØLAND S. S.,
SEMB A. G.,
HANSTEEN V.,
GJERTSEN E.,
UELAND T.,
BROSSTAD F.,
SOLUM N.O.,
AUKRUST P.
Publication year - 2006
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2006.02131.x
Subject(s) - clopidogrel , chemokine , peripheral blood mononuclear cell , platelet activation , medicine , platelet , immunology , pharmacology , inflammation , aspirin , chemistry , in vitro , biochemistry
Summary. 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 r egulated on a ctivation n ormally T ‐cell e xpressed and s ecreted (RANTES) chemokines and macrophage inflammatory peptide (MIP)‐1 β 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, β ‐thromboglobulin) during clopidogrel therapy; (iii) in contrast, clopidogrel significantly up‐regulated the gene expression of RANTES and MIP‐1 β in PBMC, while no changes were found in the placebo group; (iv) a stable adenosine 5′‐diphosphate metabolite attenuated the release of MIP‐1 β , 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.