The IkB kinase inhibitor nuclear factor-kB essential modulator–binding domain peptide for inhibition of balloon injury-induced neointimal formation

Grassia, G. et al. (2010) The IkB kinase inhibitor nuclear factor-kB essential modulator–binding domain peptide for inhibition of balloon injury-induced neointimal formation. Arteriosclerosis, Thrombosis, and Vascular Biology, 30(12), pp. 2458-2466. (doi:10.1161/ATVBAHA.110.215467)

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Abstract

Objective—The activation of nuclear factor-kB (NF-kB) is a crucial step in the arterial wall’s response to injury. The identification and characterization of the NF-kB essential modulator– binding domain (NBD) peptide, which can block the activation of the IkB kinase complex, have provided an opportunity to selectively abrogate the inflammation-induced activation of NF-kB. The aim of the present study was to evaluate the effect of the NBD peptide on neointimal formation.<br></br> Methods and Results—In the rat carotid artery balloon angioplasty model, local treatment with the NBD peptide (300 microg/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-kB 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 micromol/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 microg/site) reduced wire-induced neointimal formation at day 28 (by 47%; P<0.01).<br></br> Conclusion—The NBD peptide reduces neointimal formation and smooth muscle cell proliferation/migration, both effects associated with the inhibition of NF-kB activation.

Item Type:Articles
Keywords:Angioplasty; pharmacology; vascular biology; NEMO binding domain peptide; nuclear factor-kb
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Maffia, Dr Pasquale and Grassia, Dr Gianluca and Kennedy, Dr Simon
Authors: 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., and Ialenti, A.
Subjects:R Medicine > RZ Other systems of medicine
R Medicine > RM Therapeutics. Pharmacology
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Arteriosclerosis, Thrombosis, and Vascular Biology
Publisher:American Heart Association
ISSN:1079-5642
ISSN (Online):1524-4636
Published Online:07 October 2010
Copyright Holders:Copyright © 2010 American Heart Association
First Published:First published in Arteriosclerosis, Thrombosis and Vascular Biology 30(12):2458-2466
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
418441Capacity Building Award in Integrative Mammalian BiologyMargaret MacLeanBiotechnology and Biological Sciences Research Council (BBSRC)BB/E527071/1Institute of Cardiovascular and Medical Sciences