title: Platelet and leukocyte ROS production and lipoperoxidation are associated with high platelet reactivity in Non-ST elevation myocardial infarction (NSTEMI) patients on dual antiplatelet treatment.
abstract: BACKGROUND
  High platelet reactivity (HPR) on dual antiplatelet therapy is a risk factor for adverse vascular events in acute coronary syndrome (ACS) patients. Several studies have shown that reactive oxygen species (ROS) may be involved in modulating platelet function.
  
  
  METHODS
  In Non-ST elevation myocardial infarction (NSTEMI) patients (n = 132) undergoing percutaneous coronary intervention (PCI) on dual antiplatelet therapy blood samples were collected within 24 h from 600 mg clopidogrel loading dose. Platelet reactivity was assessed by light transmission aggregometry using 10 μM ADP, 1 mM arachidonic acid (AA) and 2 μg/ml collagen. ROS production and lipoperoxidation of circulating cells were determined. by FACSCanto flow cytometry. In these patients, we investigated: 1) the relationship between the amount of cellular ROS production/lipoperoxidation and platelet reactivity; 2) the association of cellular ROS production with the presence of high platelet reactivity to ADP and arachidonic acid (AA).
  
  
  RESULTS
  Significantly higher levels of platelet and leukocyte-derived ROS were detected in 49 dual HPR (with platelet aggregation by AA ≥ 20% and by ADP ≥ 70%) compared to non-HPR patients (n = 49) [Platelet-derived ROS: +142%; Leukocyte-derived ROS: +14%, p < 0.0001]. Similarly, dual HPR patients had significantly higher platelet and leukocyte lipoperoxidation than non-HPR patients [Platelet lipoperoxidation: +131%; Leukocyte lipoperoxidation: +14%, p < 0.001]. After adjustment for several potential confounders, platelet-, leukocyte-derived ROS and platelet and leukocyte lipoperoxidation remained significantly associated to dual HPR. The significant predictors of ADP, AA, and collagen platelet aggregation at multiple linear regression analysis, after adjusting for age, cardiovascular risk factors, procedural parameter, medications, leukocyte number and MPV, were platelet-, leukocyte-derived ROS and platelet and leukocyte lipoperoxidation (p < 001).
  
  
  CONCLUSIONS
  Our results demonstrate that in NSTEMI patients on dual antiplatelet therapy, ROS production by and lipoperoxidation of platelets are strictly correlated to the different pathways of platelet aggregation and that ROS production and lipoperoxidation of platelets and leukocytes are predictors of non responsiveness to dual antiplatelet treatment.
authors.affiliation: Department of Experimental and Clinical Medicine, University of Florence, Italy; Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Florence, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Becatti
authors.forename: Claudia
authors.initials: C
authors.lastname: Fiorillo
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Gori
authors.forename: Rossella
authors.initials: R
authors.lastname: Marcucci
authors.forename: Rita
authors.initials: R
authors.lastname: Paniccia
authors.forename: Betti
authors.initials: B
authors.lastname: Giusti
authors.forename: Francesco
authors.initials: F
authors.lastname: Violi
authors.forename: Pasquale
authors.initials: P
authors.lastname: Pignatelli
authors.forename: Gian Franco
authors.initials: GF
authors.lastname: Gensini
authors.forename: Rosanna
authors.initials: R
authors.lastname: Abbate
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000008:administration & dosage*; D001792:Blood Platelets / Q000187:drug effects*; D002469:Cell Separation; D000077144:Clopidogrel; D004334:Drug Administration Schedule; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007962:Leukocytes / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000378:metabolism*; D009391:Nephelometry and Turbidimetry; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D017382:Reactive Oxygen Species; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D010975:Platelet Aggregation Inhibitors; D017382:Reactive Oxygen Species; D000077144:Clopidogrel; D013988:Ticlopidine; D001241:Aspirin
keywords: High platelet reactivity; Leukocytes; Lipoperoxidation; ROS production