title: Inflammatory and antioxidant pattern unbalance in "clopidogrel-resistant" patients during acute coronary syndrome.
abstract: 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.
  
  
  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.
authors: National Research Council, Institute of Clinical Physiology, Cardiothoracic and Vascular Department, Niguarda Ca' Granda Hospital, Piazza Ospedale Maggiore 3, 20162 Milan, Italy.
authors: Raffaele
authors: 0000-0002-4471-2339
authors: R
authors: Caruso
authors: National Research Council, Institute of Clinical Physiology, Via Moruzzi 1, 56124 Pisa, Italy.
authors: Silvia
authors: 0000-0003-3831-4200
authors: S
authors: Rocchiccioli
authors: Department of Invasive Cardiology 1, Careggi Hospital, University of Florence, Largo Brambilla 3, 50134 Florence, Italy ; Department of Invasive Cardiology 1, Careggi Hospital, Largo Brambilla 3, 50134 Florence, Italy ; IRCCS, Fondazione Don Gnocchi, Via di Scandicci 269, 50143 Firenze, Italy.
authors: Anna Maria
authors: AM
authors: Gori
authors: National Research Council, Institute of Clinical Physiology, Via Moruzzi 1, 56124 Pisa, Italy ; Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 5, 56100 Pisa, Italy.
authors: Antonella
authors: A
authors: Cecchettini
authors: Department of Invasive Cardiology 1, Careggi Hospital, University of Florence, Largo Brambilla 3, 50134 Florence, Italy.
authors: Betti
authors: 0000-0002-8708-9444
authors: B
authors: Giusti
authors: Department of Invasive Cardiology 1, Careggi Hospital, University of Florence, Largo Brambilla 3, 50134 Florence, Italy.
authors: Guido
authors: G
authors: Parodi
authors: National Research Council, Institute of Clinical Physiology, Cardiothoracic and Vascular Department, Niguarda Ca' Granda Hospital, Piazza Ospedale Maggiore 3, 20162 Milan, Italy.
authors: Lorena
authors: 0000-0002-7429-8706
authors: L
authors: Cozzi
authors: Department of Invasive Cardiology 1, Careggi Hospital, University of Florence, Largo Brambilla 3, 50134 Florence, Italy.
authors: Rossella
authors: R
authors: Marcucci
authors: National Research Council, Institute of Clinical Physiology, Cardiothoracic and Vascular Department, Niguarda Ca' Granda Hospital, Piazza Ospedale Maggiore 3, 20162 Milan, Italy.
authors: Marina
authors: M
authors: Parolini
authors: Department of Invasive Cardiology 1, Careggi Hospital, University of Florence, Largo Brambilla 3, 50134 Florence, Italy.
authors: Ilaria
authors: I
authors: Romagnuolo
authors: National Research Council, Institute of Clinical Physiology, Via Moruzzi 1, 56124 Pisa, Italy.
authors: Lorenzo
authors: L
authors: Citti
authors: Department of Invasive Cardiology 1, Careggi Hospital, University of Florence, Largo Brambilla 3, 50134 Florence, Italy.
authors: Rosanna
authors: R
authors: Abbate
authors: National Research Council, Institute of Clinical Physiology, Cardiothoracic and Vascular Department, Niguarda Ca' Granda Hospital, Piazza Ospedale Maggiore 3, 20162 Milan, Italy ; National Research Council, Institute of Clinical Physiology, Via Moruzzi 1, 56124 Pisa, Italy.
authors: Oberdan
authors: 0000-0003-2459-1047
authors: O
authors: Parodi
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D000975:Antioxidants / Q000378:metabolism*; D054407:Chemokine CCL4 / Q000502:physiology; D000077144:Clopidogrel; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D040901:Proteomics; D017382:Reactive Oxygen Species / Q000378:metabolism; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; C066507:CCL4 protein, human; D054407:Chemokine CCL4; D015850:Interleukin-6; D010975:Platelet Aggregation Inhibitors; D017382:Reactive Oxygen Species; D000077144:Clopidogrel; D013988:Ticlopidine