Objective-: Platelets undergoing anoxia-reoxygenation (AR) simultaneously increase reactive oxygen species (ROS) and thromboxane (Tx) B2. Our aim was to assess whether there is an interplay between activation of NOX2, the catalytic subunit of NADPH oxidase, and platelet TxB2 in vitro and in vivo. Methods and 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 TxB2 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 TxA2 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 TxB2, 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. Conclusion-: AR is associated with overproduction of platelet TxB2 and isoprostanes, which is dependent on NOX2-dependent ROS generation. Low doses of aspirin are unable to prevent TxB2 formation in patients who undergo PCI. © 2011 American Heart Association, Inc.

Anoxia-reoxygenation enhances platelet thromboxane A2 production via reactive oxygen species-generated NOX2: Effect in patients undergoing elective percutaneous coronary intervention / Basili, S.; Pignatelli, P.; Tanzilli, G.; Mangieri, E.; Carnevale, R.; Nocella, C.; Di Santo, S.; Pastori, D.; Ferroni, P.; Violi, F.. - In: ARTERIOSCLEROSIS, THROMBOSIS, AND VASCULAR BIOLOGY. - ISSN 1079-5642. - 31:8(2011), pp. 1766-1771. [10.1161/ATVBAHA.111.227959]

Anoxia-reoxygenation enhances platelet thromboxane A2 production via reactive oxygen species-generated NOX2: Effect in patients undergoing elective percutaneous coronary intervention

Basili S.
Co-primo
;
Pignatelli P.
Co-primo
;
Tanzilli G.;Mangieri E.;Carnevale R.;Nocella C.;Di Santo S.;Pastori D.;Ferroni P.;Violi F.
Ultimo
2011

Abstract

Objective-: Platelets undergoing anoxia-reoxygenation (AR) simultaneously increase reactive oxygen species (ROS) and thromboxane (Tx) B2. Our aim was to assess whether there is an interplay between activation of NOX2, the catalytic subunit of NADPH oxidase, and platelet TxB2 in vitro and in vivo. Methods and 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 TxB2 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 TxA2 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 TxB2, 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. Conclusion-: AR is associated with overproduction of platelet TxB2 and isoprostanes, which is dependent on NOX2-dependent ROS generation. Low doses of aspirin are unable to prevent TxB2 formation in patients who undergo PCI. © 2011 American Heart Association, Inc.
aspirin; isoprostanes; NOX2; thromboxanes; vitamin C; Aged; Blood Platelets; Female; Humans; Hypoxia; In Vitro Techniques; Isoprostanes; Male; Membrane Glycoproteins; Middle Aged; Myocardial Reperfusion; Myocardial Reperfusion Injury; NADPH Oxidase 2; NADPH Oxidases; Oxidative Stress; Platelet Activation; Reactive Oxygen Species; Thromboxane A2; Angioplasty, Balloon, Coronary
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Anoxia-reoxygenation enhances platelet thromboxane A2 production via reactive oxygen species-generated NOX2: Effect in patients undergoing elective percutaneous coronary intervention / Basili, S.; Pignatelli, P.; Tanzilli, G.; Mangieri, E.; Carnevale, R.; Nocella, C.; Di Santo, S.; Pastori, D.; Ferroni, P.; Violi, F.. - In: ARTERIOSCLEROSIS, THROMBOSIS, AND VASCULAR BIOLOGY. - ISSN 1079-5642. - 31:8(2011), pp. 1766-1771. [10.1161/ATVBAHA.111.227959]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1345285
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