The NF kappa B inhibitory peptide, I kappa B alpha, 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 influ ence vascular smooth muscle cell (VSMC) growth and contribute to atherogene sis. Nuclear factor-kappa B (NF kappa B) is a central transcription factor important in mediating stress and inflammatory-induced signals. We hypothes ized 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 fac tor (FGF) and tumor necrosis factor-alpha (TNF), and proliferation was quan tified by a colormetric assay. The influence of NF kappa B on VSMC prolifer ation was examined by both nonspecific NF kappa B blockade with calpain inh ibitor-1 (CI-1) and dexamethasone (Dex) and specific NF kappa B blockade wi th 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 proli feration of unstimulated VSMC. However, both FGF- and TNF-stimulated VSMC p roliferation was inhibited to the level of control with CI-1, Dex, and lipo somal 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 e ndogenous inhibitory proteins such as I kappa B alpha may represent a novel , therapeutically accessible method for selective transcriptional suppressi on in the response to vascular injury.