Object-Platelet isoprostane 8-ISO-prostaglandin F2␣ (8-iso-PGF2␣), a proaggregating molecule, is believed to derive from nonenzymatic oxidation of arachidonic acid. We hypothesized that NADPH is implicated in isoprostane formation and platelet activation. Methods and Results-We studied 8-iso-PGF2␣ in platelets from 8 male patients with hereditary deficiency of gp91 phox , the catalytic subunit of NADPH oxidase, and 8 male controls. On stimulation, platelets from controls produced 8-iso-PGF2␣, which was inhibited Ϫ8% by aspirin and Ϫ58% by a specific inhibitor of gp91 phox . Platelets from patients with gp91phox hereditary deficiency had normal thromboxane A 2 formation but marked 8-iso-PGF2␣ reduction compared with controls. In normal platelets incubated with a gp91 phox inhibitor or with SQ29548, a thromboxane A 2 /isoprostane receptor inhibitor, platelet recruitment, an in vitro model of thrombus growth, was reduced by 44% and 64%, respectively; a lower effect (Ϫ17%) was seen with aspirin. Moreover, thrombus formation under shear stress (blood perfusion at the wall shear rate of 1500 s Ϫ1 ) was reduced in samples in which isoprostane formation was inhibited by NADPH oxidase inhibitors. In gp91 phox -deficient patients, agonist-induced platelet aggregation was within the normal range, whereas platelet recruitment was reduced compared with controls. Incubation of platelets from gp91 phox -deficient patients with 8-iso-PGF2␣ dose-dependently (1 to 100 pmol/L) increased platelet recruitment by mobilizing platelet Ca 2ϩ and activating gpIIb/IIIa; a further increase in platelet recruitment was detected by platelet coincubation with L-NAME, an inhibitor of NO synthase. Conclusion-This

Background-Statins exert an antithrombotic effect in patients at risk of or with acute thrombosis, but no study has investigated whether this effect is immediate and whether there is an underline mechanism. Methods and Results-Patients with hypercholesterolemia were randomly allocated to a Mediterranean diet with low cholesterol intake (Ͻ300 mg/d; nϭ15) or atorvastatin (40 mg/d; nϭ15). Oxidative stress, as assessed by serum Nox2 and urinary isoprostanes, and platelet activation, as assessed by platelet recruitment, platelet isoprostanes, and thromboxane A 2 , platelet Nox2, Rac1, p47

LPS may be responsible for platelet activation and potentially contributes to thrombotic complications occurring in cirrhosis. (Hepatology 2017;65:571-581).