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Craig H. Selzman
Robert C. McIntyre, Jr
Alden H. Harken
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Ann Thorac Surg 1999;67:1227-1231
© 1999 The Society of Thoracic Surgeons


Original Articles

The NF{kappa}B inhibitory peptide, I{kappa}B{alpha}, prevents human vascular smooth muscle proliferation

Craig H. Selzman, MDa, Brian D. Shames, MDa, Robert C. McIntyre, Jr, MDa, Anirban Banerjee, PhDa, Alden H. Harken, MDa

a Department of Surgery, University of Colorado Health Sciences Center, Denver, Colorado, USA

Address reprint requests to Dr Selzman, Dept of Surgery, University of Colorado Health Sciences Center, Campus Box C-320, 4200 East Ninth Ave, Denver, CO 80262
e-mail: craig.selzman{at}UCHSC.edu

Presented at the Thirty-fifth Annual Meeting of The Society of Thoracic Surgeons, San Antonio, TX, January 25–27, 1999.

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.




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