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 (NF kappa B) is a central transcription factor important in mediating stress and inflammatory-induced signals. We hypothesized that strategies aimed at inhibiting NF kappa B would abrogate mitogen-induced human VSMC proliferation. Methods. Human aortic VSMC were stimulated with basic fibroblast growth factor (FGF) and tumor necrosis factor-alpha (TNF), and proliferation was quantified by a colormetric assay. The influence of NF kappa B on VSMC proliferation was examined by both nonspecific NF kappa B blockade with calpain inhibitor-1 (CI-1) and dexamethasone (Dex) and specific NF kappa B blockade with liposomal delivery of the NF kappa B inhibitory peptide, I kappa B alpha. Results. FGF and TNF induced concentration-dependent VSMC proliferation (p < 0.002). Neither CI-1, Dex, nor liposomal I kappa B alpha 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 I kappa B alpha (p < 0.001). Conclusion. The mitogenic effect of FGF and TNF on human arterial VSMC may be prevented by inhibiting NF kappa B. Furthermore, liposomal delivery of endogenous inhibitory proteins such as I kappa B alpha may represent a novel, therapeutically accessible method for selective transcriptional suppression in the response to vascular injury.