title: Anoxia-reoxygenation enhances platelet thromboxane A2 production via reactive oxygen species-generated NOX2: effect in patients undergoing elective percutaneous coronary intervention.
abstract: OBJECTIVE
  Platelets undergoing anoxia-reoxygenation (AR) simultaneously increase reactive oxygen species (ROS) and thromboxane (Tx) B(2). Our aim was to assess whether there is an interplay between activation of NOX2, the catalytic subunit of NADPH oxidase, and platelet TxB(2) in vitro and in vivo.
  
  
  RESULTS
  Platelets that underwent AR had enhanced ROS. This was associated with NOX2 activation and was inhibited by incubation with NOX2-blocking peptide. AR was associated with TxB(2) and isoprostane production, which were inhibited by NOX2-blocking peptide, vitamin C, and the inhibitor of phospholipase A(2). Platelet incubation with 100 μmol/L aspirin fully prevented AR-induced TxA(2) but did not affect isoprostane production. We included 56 aspirin-treated patients undergoing elective percutaneous coronary intervention (PCI) who were randomly allocated to receive either placebo or intravenous infusion of 1 g of vitamin C. Blood TxB(2), isoprostanes, and soluble NOX2-derived peptide, a marker of systemic NADPH oxidase activation, significantly increased at 60 and 120 minutes after PCI in placebo-treated but not in vitamin C-treated patients.
  
  
  CONCLUSIONS
  AR is associated with overproduction of platelet TxB(2) and isoprostanes, which is dependent on NOX2-dependent ROS generation. Low doses of aspirin are unable to prevent TxB(2) formation in patients who undergo PCI.
authors.affiliation: Divisione I Clinica Medica, Sapienza University of Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Basili
authors.forename: Pasquale
authors.initials: P
authors.lastname: Pignatelli
authors.forename: Gaetano
authors.initials: G
authors.lastname: Tanzilli
authors.forename: Enrico
authors.initials: E
authors.lastname: Mangieri
authors.forename: Roberto
authors.initials: R
authors.lastname: Carnevale
authors.forename: Cristina
authors.initials: C
authors.lastname: Nocella
authors.forename: Serena
authors.initials: S
authors.lastname: Di Santo
authors.forename: Daniele
authors.initials: D
authors.lastname: Pastori
authors.forename: Patrizia
authors.initials: P
authors.lastname: Ferroni
authors.forename: Francesco
authors.initials: F
authors.lastname: Violi
mesh_terms: D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D001792:Blood Platelets / Q000378:metabolism*; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000097:blood*; D066298:In Vitro Techniques; D028421:Isoprostanes / Q000097:blood; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood*; D008875:Middle Aged; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000097:blood; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000097:blood*; D018384:Oxidative Stress; D015539:Platelet Activation; D017382:Reactive Oxygen Species / Q000097:blood; D013928:Thromboxane A2 / Q000097:blood*
chemical_list: D028421:Isoprostanes; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; D013928:Thromboxane A2; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases