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) (PMID:20930169)
|
Text
46018.pdf - Accepted Version 8MB |
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: | Kennedy, Professor Simon and Maffia, Professor Pasquale and Grassia, Dr Gianluca |
| 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 > School of Cardiovascular & Metabolic Health College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| 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 |
| Related URLs: |
University Staff: Request a correction | Enlighten Editors: Update this record
Funder and Project Information
Funder and Project Information