The IκB Kinase Inhibitor Nuclear Factor-κB Essential Modulator-Binding Domain Peptide for Inhibition of Injury-Induced Neointimal Formation

Objective-The activation of nuclear factor-kappa B (NF-kappa B) is a crucial step in the arterial wall's response to injury. The identification and characterization of the NF-kappa B essential modulator-binding domain (NBD) peptide, which can block the activation of the I kappa B kinase complex, have provided an opportunity to selectively abrogate the inflammation-induced activation of NF-kappa B. 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 mu g/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 < 0.01) at day 14. These effects were associated with a significant reduction of NF-kappa B 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 mu mol/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 mu g/site) reduced wire-induced neointimal formation at day 28 (by 47%; P < 0.01). Conclusion-The NBD peptide reduces neointimal formation and smooth muscle cell proliferation/migration, both effects associated with the inhibition of NF-kappa B activation. (Arterioscler Thromb Vasc Biol. 2010;30:2458-2466.)