Relative contribution of the TNF-alpha receptors to murine intimal hyperplasia.
Tumor necrosis factor-alpha (TNF-alpha) is an important mediator in the inflammatory response to vascular injury. The present study sought to determine the relative contribution of each TNF-alpha 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-kappaB 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-kappaB may provide a mechanism by which p55-mediated IH is attenuated.
Zimmerman
Michael A
MA
Divisions of Cardiothoracic Surgery and Infectious Disease, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
Reznikov
Leonid L
LL
Sorensen
Amy C
AC
Selzman
Craig H
CH
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D020212:Carotid Artery Injuries / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006965:Hyperplasia / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D017539:Tunica Intima / Q000293:injuries / Q000378:metabolism* / Q000473:pathology*
D015703:Antigens, CD; D016328:NF-kappa B; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha