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2013-02-20

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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/181519

Inhibition of nicotinamide phosphoribosyltransferase reduces neutrophil-mediated injury in myocardial infarction

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https://doi.org/10.1089/ars.2011.4487

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Aims: nicotinamide phosphoribosyltransferase (Nampt) is a key enzyme for nicotinamide adenine dinucleotide (NAD(+)) biosynthesis, and recent evidence indicates its role in inflammatory processes. Here, we investigated the potential effects of pharmacological Nampt inhibition with FK866 in a mouse myocardial ischemia/reperfusion model. In vivo and ex vivo mouse myocardial ischemia/reperfusion procedures were performed. Results: treatment with FK866 reduced myocardial infarct size, neutrophil infiltration, and reactive oxygen species (ROS) generation within infarcted hearts in vivo in a mouse model of ischemia and reperfusion. The benefit of FK866 was not shown in the Langendorff model (ex vivo model of working heart without circulating leukocytes), suggesting a direct involvement of these cells in cardiac injury. Sera from FK866-treated mice showed reduced circulating levels of the neutrophil chemoattractant CXCL2 and impaired capacity to prime migration of these cells in vitro. The release of CXCL8 (human homolog of murine chemokine CXCL2) by human peripheral blood mononuclear cells (PBMCs) and Jurkat cells was also reduced by FK866, as well as by sirtuin (SIRT) inhibitors and SIRT6 silencing, implying a pivotal role for this NAD(+)-dependent deacetylase in the production of this chemokine. Innovation: the pharmacological inhibition of Nampt might represent an effective approach to reduce neutrophilic inflammation- and oxidative stress-mediated tissue damage in early phases of reperfusion after a myocardial infarction. Conclusions: nampt inhibition appears as a new strategy to dampen CXCL2-induced neutrophil recruitment and thereby reduce neutrophil-mediated tissue injury in mice.

Matèries

Infart de miocardi, Neutròfils, Efectes secundaris dels medicaments

Matèries (anglès)

Myocardial infarction, Neutrophils, Drug side effects

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Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia)
<b>Publicacions de projectes de recerca finançats per la UE</b>

Citació

MONTECUCCO, Fabrizio, BAUER, Inga, BRAUNERSREUTHER, Vincent, BRUZZONE, Santina, AKHMEDOV, Alexander, LÜSCHER, Thomas f., SPEER, Timo, POGGI, Alessandro, MANNINO, Elena, PELLI, Graziano, GALAN, Katia, BERTOLOTTO, Maria, LENGLET, Sébastien, GARUTI, Anna, MONTESSUIT, Christophe, LERCH, René, PELLIEUX, Corinne, VUILLEUMIER, Nicolas, DALLEGRI, Franco, MAGE, Jacqueline, SEBASTIAN, Carlos, MOSTOSLAVSKY, Raúl, GAYET-AGERON, Angèle, PATRONE, Franco, MACH, François, NENCIONI, Alessio. Inhibition of nicotinamide phosphoribosyltransferase reduces neutrophil-mediated injury in myocardial infarction. _Antioxidants & Redox Signaling_. 2013. Vol. 18, núm. 6, pàgs. 630-641. [consulta: 23 de gener de 2026]. ISSN: 1523-0864. [Disponible a: https://hdl.handle.net/2445/181519]

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