The NFκB inhibitory peptide, IκBα, prevents human vascular smooth muscle proliferation

Background. Vessel injury results in an inflammatory response characterized by the elaboration of cytokines and growth factors, which ultimately influence vascular smooth muscle cell (VSMC) growth and contribute to atherogenesis. Nuclear factor-kappa B (NFκB) is a central transcription factor important in mediating stress and inflammatory-induced signals. We hypothesized that strategies aimed at inhibiting NFκB would abrogate mitogen-induced human VSMC proliferation. Methods. Human aortic VSMC were stimulated with basic fibroblast growth factor (FGF) and tumor necrosis factor-α (TNF), and proliferation was quantified by a colormetric assay. The influence of NFκB on VSMC proliferation was examined by both nonspecific NFκB blockade with calpain inhibitor-1 (CI-1) and dexamethasone (Dex) and specific NFκB blockade with liposomal delivery of the NFκB inhibitory peptide, IκBα. Results. FGF and TNF induced concentration-dependent VSMC proliferation (p< 0.002). Neither CI-1, Dex, nor liposomal IκBα influenced proliferation of unstimulated VSMC. However, both FGF- and TNF-stimulated VSMC proliferation was inhibited to the level of control with CI-1, Dex, and liposomal IκBα (p< 0.001). Conclusion. The mitogenic effect of FGF and TNF on human arterial VSMC may be prevented by inhibiting NFκB. Furthermore, liposomal delivery of endogenous inhibitory proteins such as IκBα may represent a novel, therapeutically accessible method for selective transcriptional suppression in the response to vascular injury.