Experimental studies have suggested that TNFalpha, 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 TNFalpha 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 1, 9 in class 11, 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 O-2 production, and plasma TNFalpha. In vivo results showed increased platelet O-2(-) production and plasma TNFalpha levels in NYHA class III-IV compared with that in controls or in NYHA I-II (p<0,001); platelet O-2(-) production correlated significantly (R=0,6; p<0,0 1) with TNF&alpha; plasma levels. In vitro studies showed TNF&alpha; dose-dependently (5-40 pg/ml) induced platelet O-2(-) production, and that this effect was significantly inhibited by its specific inhibitor WP9QY (I muM); aspirin (100 muM),AACOCF(3), a specific PLA(2) inhibitor (14 muM), and DPI, an inhibitor of NADPH oxidase, significantly inhibited TNFalpha-mediated platelet O-2(-) production. This study suggests that in patients with heart failure, enhanced platelet O-2(-) production is mediated by TNFalpha via activation of arachidonic acid and NADPH oxidase pathways.

Enhanced TNF alpha and oxidative stress in patients with heart failure: effect of TNF alpha on platelet O-2(-) production / DE BIASE, Luciano; Pignatelli, Pasquale; Lenti, Luisa; Tocci, Giuliano; Fabiana, Piccioni; Riondino, Silvia; Pulcinelli, FABIO MARIA; Rubattu, Speranza Donatella; Volpe, Massimo; Violi, Francesco. - In: THROMBOSIS AND HAEMOSTASIS. - ISSN 0340-6245. - STAMPA. - 90:2(2003), pp. 317-325. [10.1160/th03-02-0105]

Enhanced TNF alpha and oxidative stress in patients with heart failure: effect of TNF alpha on platelet O-2(-) production

DE BIASE, Luciano;PIGNATELLI, Pasquale;LENTI, Luisa;TOCCI, GIULIANO;RIONDINO, Silvia;PULCINELLI, FABIO MARIA;RUBATTU, Speranza Donatella;VOLPE, Massimo;VIOLI, Francesco
2003

Abstract

Experimental studies have suggested that TNFalpha, 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 TNFalpha 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 1, 9 in class 11, 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 O-2 production, and plasma TNFalpha. In vivo results showed increased platelet O-2(-) production and plasma TNFalpha levels in NYHA class III-IV compared with that in controls or in NYHA I-II (p<0,001); platelet O-2(-) production correlated significantly (R=0,6; p<0,0 1) with TNFα plasma levels. In vitro studies showed TNFα dose-dependently (5-40 pg/ml) induced platelet O-2(-) production, and that this effect was significantly inhibited by its specific inhibitor WP9QY (I muM); aspirin (100 muM),AACOCF(3), a specific PLA(2) inhibitor (14 muM), and DPI, an inhibitor of NADPH oxidase, significantly inhibited TNFalpha-mediated platelet O-2(-) production. This study suggests that in patients with heart failure, enhanced platelet O-2(-) production is mediated by TNFalpha via activation of arachidonic acid and NADPH oxidase pathways.
2003
heart failure; oxidative stress; platelets; tnf alpha
01 Pubblicazione su rivista::01a Articolo in rivista
Enhanced TNF alpha and oxidative stress in patients with heart failure: effect of TNF alpha on platelet O-2(-) production / DE BIASE, Luciano; Pignatelli, Pasquale; Lenti, Luisa; Tocci, Giuliano; Fabiana, Piccioni; Riondino, Silvia; Pulcinelli, FABIO MARIA; Rubattu, Speranza Donatella; Volpe, Massimo; Violi, Francesco. - In: THROMBOSIS AND HAEMOSTASIS. - ISSN 0340-6245. - STAMPA. - 90:2(2003), pp. 317-325. [10.1160/th03-02-0105]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/363662
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