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

Divisions of 1 Cardiothoracic Surgery and 2 Infectious Disease, University of Colorado Health Sciences Center, Denver, Colorado 80262 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. vasculature; restenosis; carotid arteries