Role of nuclear factor-kappaB in a rat model of vascular injury

In this study we have investigated the relationship between neointima formation and NF-kappaB activation in a model of endothelial denudation of rat carotid artery (balloon angioplasty) using the antioxidant pyrrolidine dithiocarbamate as inhibitor of NF-kappaB activation. Furthermore, we have correlated NF-kappaB activation to the expression of inducible isoforms of both nitric oxide synthase (iNOS) and cyclooxygenase (COX-2) in injured carotids. In control group a significant proliferation of neointima was observed 14 days after balloon angioplasty, which was correlated to an increase of NF-kappaB/DNA binding activity as well as p50/p65 nuclear levels compared to those observed in the carotids from naive or sham-operated rats. Furthermore, NF-kappaB activation was correlated to increased iNOS and COX-2, but not beta-actin, protein expression. Treatment of rats for 14 days with the antioxidant agent pyrrolidine dithiocarbamate (50, 100, 200 mg/kg per os and day) caused a significant inhibition of all the parameters assayed, except beta-actin protein expression. These results indicate that prevention of NF-kappaB activation may lead to the inhibition of neointima formation and suggest that antioxidant agents may have therapeutic relevance for the prevention of human restenosis.