title: Platelet isoprostane overproduction in diabetic patients treated with aspirin.
abstract: Aspirin modestly influences cardiovascular events in patients with type 2 diabetes mellitus (T2DM), but the reason is unclear. The aim of the study was to determine whether in T2DM patients aspirin enhances platelet isoprostanes, which are eicosanoids with proaggregating properties derived from arachidonic acid oxidation by platelet NOX2, the catalytic subunit of reduced NAD phosphate oxidase. A cross-sectional study was performed comparing T2DM patients, treated (n = 50) or not treated (n = 50) with 100 mg/day aspirin, with 100 nondiabetic patients, matched for age, sex, atherosclerosis risk factors, and aspirin treatment. A short-term (7 days) treatment with 100 mg/day aspirin also was performed in 36 aspirin-free diabetic and nondiabetic patients. Higher platelet recruitment, platelet isoprostane, and NOX2 activation was found in diabetic versus nondiabetic patients and in aspirin-treated diabetic patients versus nontreated patients (P < 0.001). Platelet thromboxane (Tx) A(2) (P < 0.001) was inhibited in all aspirin-treated patients. In the interventional study, aspirin similarly inhibited platelet TxA(2) in diabetic and nondiabetic patients (P < 0.001). Platelet recruitment, isoprostane levels, and NOX2 activation showed a parallel increase in diabetic patients (P < 0.001) and no changes in nondiabetic patients. These findings suggest that in aspirin-treated diabetic patients, oxidative stress-mediated platelet isoprostane overproduction is associated with enhanced platelet recruitment, an effect that mitigates aspirin-mediated TxA(2) inhibition.
authors.affiliation: I Clinica Medica, Sapienza University of Rome, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Cangemi
authors.forename: Pasquale
authors.initials: P
authors.lastname: Pignatelli
authors.forename: Roberto
authors.initials: R
authors.lastname: Carnevale
authors.forename: Carmen
authors.initials: C
authors.lastname: Nigro
authors.forename: Marco
authors.initials: M
authors.lastname: Proietti
authors.forename: Francesco
authors.initials: F
authors.lastname: Angelico
authors.forename: Davide
authors.initials: D
authors.lastname: Lauro
authors.forename: Stefania
authors.initials: S
authors.lastname: Basili
authors.forename: Francesco
authors.initials: F
authors.lastname: Violi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D003430:Cross-Sectional Studies; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D028421:Isoprostanes / Q000378:metabolism*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008875:Middle Aged; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism; D013931:Thromboxanes / Q000378:metabolism*
chemical_list: D016861:Cyclooxygenase Inhibitors; D028421:Isoprostanes; D008562:Membrane Glycoproteins; D013931:Thromboxanes; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D001241:Aspirin