Relative contribution of the TNF-α receptors to murine intimal hyperplasia

Tumor necrosis factor- (TNF-) is an important mediator in the inflammatory response to vascular injury. The present study sought to determine the relative contribution of each TNF- receptor subtype (p55 and p75) to intimal hyperplasia (IH) and characterize the mechanisms of transcriptional regulation after vascular injury. A murine model of wire carotid arterial injury was employed to induce IH in wild-type (WT), p55-deficient (p55/), and p75-deficient (p75/) mice. Compared with injured WT and p75/ animals, p55/ mice demonstrated a twofold reduction in IH. Additionally, p55/ mice demonstrated a decrease in expression of nuclear factor-B mRNA and protein. These observations suggest an important role for the p55 receptor in IH after mechanical endoluminal injury. Suppression of the transcriptional activator nuclear factor-B may provide a mechanism by which p55-mediated IH is attenuated.