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Luciano De Biase, Pasquale Pignatelli, Luisa Lenti, Giuliano Tocci, Fabiana Piccioni, Silvia Riondino, Fabio M. Pulcinelli, Speranza Rubattu, Massimo Volpe, Francesco Violi
Enhanced TNF and oxidative stress in patients with heart failure: effect of TNF on platelet O2 production
Experimental studies have suggested that TNF, a pro-inflammatory cytokine, may contribute to the deterioration of cardiovascular function through various mechanisms, including the generation of reactive oxygen species. It has not yet been demonstrated whether TNF has prooxidant activity in patients with heart failure, and what the mechanism eventually resulting in this effect are. We analyzed 42 patients (38 men and 4 women, aged 26 to 74 years) with heart failure, secondary to idiopathic dilated cardiomyopathy (n=21), coronary artery disease (n=15), and valve disease (n=6), and 20 controls (18 men and 2 women, aged 49 to 67 years). Ten patients were in class I, 9 in class II, 15 in class III and 8 in class IV according to NYHA Classification. Blood samples were obtained from each patient to evaluate basal and collagen-induced platelet O2 production, and plasma TNF. In vivo results showed increased platelet O2 production and plasma TNF levels in NYHA class III-IV compared with that in controls or in NYHA I-II (p<0,001); platelet O2 production correlated significantly (R=0,6; p<0,01) with TNF plasma levels. In vitro studies showed TNF dose-dependently (540 pg/ml) induced platelet O2 production, and that this effect was significantly inhibited by its specific inhibitor, WP9QY (1 M); aspirin (100 M), AACOCF3, a specific PLA2 inhibitor (14 M), and DPI, an inhibitor of NADPH oxidase, significantly inhibited TNF-mediated platelet O2 production. This study suggests that in patients with heart failure, enhanced platelet O2 production is mediated by TNF via activation of arachidonic acid and NADPH oxidase pathways.
Thrombosis and Haemostasis, Schattauer
Print ISSN: 0340-6245
Volume: 90, 08/2003
Pages: 317 - 325