ROLE OF NUCLEAR FACTOR-KAPPA-B IN ATHEROGENESIS

Transcription factors of the nuclear factor-kappa B (NF-kappa B)/Rel f amily have an important function in the regulation of a variety of gen es involved in the inflammatory and proliferative responses of cells. Recent studies strongly indicate that the inducible transcription fact or NF-kappa B is involved in the pathogenesis of atherosclerosis. Acti vated NF-kappa B is present in the fibrotic thickened intima-media and atheromatous areas of the atherosclerotic lesion, within smooth muscl e cells, macrophages and endothelial cells, whereas little or no activ ated NF-kappa B can be detected in vessels lacking atherosclerosis. A variety of molecules have been identified in the atherosclerotic envir onment that are able to activate NF-kappa B in vitro. Furthermore, an increased expression of numerous genes known to be regulated by NF-kap pa B has been found in the atherosclerotic lesion. Possible functional implications for activated NF-kappa B in atherogenesis are discussed here. The activation and role of NF-kappa B in atherosclerosis may pro vide a model for the involvement of the transcription factor in human chronic inflammatory disease.