Abstract OBJECTIVE: The activation of nuclear factor-κB (NF-κB) is a crucial step in the arterial wall's response to injury. The identification and characterization of the NF-κB essential modulator-binding domain (NBD) peptide, which can block the activation of the IκB kinase complex, have provided an opportunity to selectively abrogate the inflammation-induced activation of NF-κB. The aim of the present study was to evaluate the effect of the NBD peptide on neointimal formation. METHODS AND RESULTS: In the rat carotid artery balloon angioplasty model, local treatment with the NBD peptide (300 μg/site) significantly reduced the number of proliferating cells at day 7 (by 40%; P<0.01) and reduced injury-induced neointimal formation (by 50%; P<0.001) at day 14. These effects were associated with a significant reduction of NF-κB activation and monocyte chemotactic protein-1 expression in the carotid arteries of rats treated with the peptide. In addition, the NBD peptide (0.01 to 1 μmol/L) reduced rat smooth muscle cell proliferation, migration, and invasion in vitro. Similar results were observed in apolipoprotein E(-/-), mice in which the NBD peptide (150 μg/site) reduced wire-induced neointimal formation at day 28 (by 47%; P<0.01). CONCLUSIONS: The NBD peptide reduces neointimal formation and smooth muscle cell proliferation/migration, both effects associated with the inhibition of NF-κB activation.

The I{kappa}B Kinase Inhibitor Nuclear Factor-{kappa}B Essential Modulator-Binding Domain Peptide for Inhibition of Balloon Injury-Induced Neointimal Formation / Grassia G.; Maddaluno M.; Musilli C.; De Stefano D.; Carnuccio R.; Di Lauro M.V.; Parratt C.A.; Kennedy S.; Di Meglio P.; Ianaro A.; Maffia P.; Parenti A.; Ialenti A.. - In: ARTERIOSCLEROSIS, THROMBOSIS, AND VASCULAR BIOLOGY. - ISSN 1079-5642. - STAMPA. - 30(12):(2010), pp. 2458-2466. [10.1161/ATVBAHA.110.215467]

The I{kappa}B Kinase Inhibitor Nuclear Factor-{kappa}B Essential Modulator-Binding Domain Peptide for Inhibition of Balloon Injury-Induced Neointimal Formation.

MUSILLI, CLAUDIA;PARENTI, ASTRID;
2010

Abstract

Abstract OBJECTIVE: The activation of nuclear factor-κB (NF-κB) is a crucial step in the arterial wall's response to injury. The identification and characterization of the NF-κB essential modulator-binding domain (NBD) peptide, which can block the activation of the IκB kinase complex, have provided an opportunity to selectively abrogate the inflammation-induced activation of NF-κB. The aim of the present study was to evaluate the effect of the NBD peptide on neointimal formation. METHODS AND RESULTS: In the rat carotid artery balloon angioplasty model, local treatment with the NBD peptide (300 μg/site) significantly reduced the number of proliferating cells at day 7 (by 40%; P<0.01) and reduced injury-induced neointimal formation (by 50%; P<0.001) at day 14. These effects were associated with a significant reduction of NF-κB activation and monocyte chemotactic protein-1 expression in the carotid arteries of rats treated with the peptide. In addition, the NBD peptide (0.01 to 1 μmol/L) reduced rat smooth muscle cell proliferation, migration, and invasion in vitro. Similar results were observed in apolipoprotein E(-/-), mice in which the NBD peptide (150 μg/site) reduced wire-induced neointimal formation at day 28 (by 47%; P<0.01). CONCLUSIONS: The NBD peptide reduces neointimal formation and smooth muscle cell proliferation/migration, both effects associated with the inhibition of NF-κB activation.
2010
30(12)
2458
2466
Grassia G.; Maddaluno M.; Musilli C.; De Stefano D.; Carnuccio R.; Di Lauro M.V.; Parratt C.A.; Kennedy S.; Di Meglio P.; Ianaro A.; Maffia P.; Parenti A.; Ialenti A.
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/394873
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