Lack of TNF-α attenuates intimal hyperplasia after mouse carotid artery injury

Abstract

This study sought to determine the influence of tumor necrosis factor-α (TNF-α) on intimal hyperplasia (IH) and characterize the mechanisms of transcriptional regulation after vascular injury. A murine model of wire carotid artery injury was employed to induce IH in wild-type (WT) and TNF-α-deficient [TNF(−/−)] animals. Three days after injury, TNF-α and nuclear factor-κB (NF-κB) protein expression was markedly increased in the injured WT carotid artery compared to control. Injury increased TNF-α and NF-κB mRNA expression 100- and 7.5-fold, respectively. Compared with WT specimens, injury in TNF(−/−) animals decreased both NF-κB mRNA and protein nearly 7.5- and 4-fold, respectively. Expression of the NF-κB-dependent cytokine monocyte chemotactic protein 1 was markedly diminished in injured TNF(−/−) animals. Finally, TNF(−/−) animals demonstrated a sevenfold reduction in IH compared with WT animals. Cumulatively, these data mechanistically link TNF-α and NF-κB in vivo and suggest an important influence of TNF-α on postinjury IH.