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Mediators of Inflammation
Volume 2015, Article ID 710123, 12 pages
Research Article

Inflammatory and Antioxidant Pattern Unbalance in “Clopidogrel-Resistant” Patients during Acute Coronary Syndrome

1National Research Council, Institute of Clinical Physiology, Cardiothoracic and Vascular Department, Niguarda Ca’ Granda Hospital, Piazza Ospedale Maggiore 3, 20162 Milan, Italy
2National Research Council, Institute of Clinical Physiology, Via Moruzzi 1, 56124 Pisa, Italy
3Department of Invasive Cardiology 1, Careggi Hospital, University of Florence, Largo Brambilla 3, 50134 Florence, Italy
4Department of Invasive Cardiology 1, Careggi Hospital, Largo Brambilla 3, 50134 Florence, Italy
5IRCCS, Fondazione Don Gnocchi, Via di Scandicci 269, 50143 Firenze, Italy
6Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 5, 56100 Pisa, Italy

Received 20 November 2014; Revised 30 January 2015; Accepted 2 March 2015

Academic Editor: Dianne Cooper

Copyright © 2015 Raffaele Caruso et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Background. In acute coronary syndrome (ACS), inflammation and redox response are associated with increased residual platelet reactivity (RPR) on clopidogrel therapy. We investigated whether clopidogrel interaction affects platelet function and modulates factors related to inflammation and oxidation in ACS patients differently responding to clopidogrel. Material and Methods. Platelet aggregation was measured in 29 ACS patients on dual (aspirin/clopidogrel) antiplatelet therapy. Nonresponders (NR) were defined as RPR ≥70% by ADP. Several inflammatory and redox parameters were assayed and platelet proteome was determined. Results. Eight (28%) out of 29 ACS patients resulted NR to clopidogrel. At 24 hours, the levels of Th2-type cytokines IL-4, IFNγ, and MCP-1 were higher in NR, while blood GSH (r-GSHbl) levels were lower in NR than responders (R). Proteomic analysis evidenced an upregulated level of platelet adhesion molecule, CD226, and a downregulation of the antioxidant peroxiredoxin-4. In R patients the proinflammatory cytokine IL-6 decreased, while the anti-inflammatory cytokine IL-1Ra increased. Conclusions. In patients with high RPR on clopidogrel therapy, an unbalance of inflammatory factors, platelet adhesion molecules, and circulatory and platelet antioxidant molecules was observed during the acute phase. Proinflammatory milieu persists in nonresponders for a long time after the acute event while antioxidant blood factors tend to conform to normal responsiveness.