Gene deletion of NF-κB p105 enhances neointima formation in a mouse model of carotid artery injury

The role of nuclear factor kappa-B (NF-kappa B) p105 for vascular inflammatory gene expression and neointima formation after arterial injury was studied. Mice carotid arteries were injured by ligation. Vascular NF-kappa B activation was monitored using a NF-kappa B luciferase reporter mouse. Mice with gene deletion of the NF-kappa B p105 subunit (p50 precursor) and the corresponding wild types were assessed for vascular gene expression and neointimal hyperplasia. NF-kappa B was activated in the injured vessel wall in wild type mice, and this was accompanied by increased expression of the proin-flammatory genes tumor necrosis factor alpha, interleukin 1 beta, and inducible nitric oxide synthase. In contrast, NF-kappa B p105 knockout mice had reduced expression of the inflammatory genes and enhanced neointima formation four weeks after ligation. Basic fibroblast growth factor (bFGF) gene expression increased after arterial ligation. A higher percentage of bFGF positive cells were found in lesions from NF-kappa B p105 knock out mice. These data indicate that the p105 subunit of NF-kappa B plays an essential role in vascular healing, and defects in NF-kappa B p105 promote neointima hyperplasia.