Lack of TNF-alpha attenuates intimal hyperplasia after mouse carotid artery injury.
This study sought to determine the influence of tumor necrosis factor-alpha (TNF-alpha) 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-alpha-deficient [TNF(-/-)] animals. Three days after injury, TNF-alpha and nuclear factor-kappaB (NF-kappaB) protein expression was markedly increased in the injured WT carotid artery compared to control. Injury increased TNF-alpha and NF-kappaB mRNA expression 100- and 7.5-fold, respectively. Compared with WT specimens, injury in TNF(-/-) animals decreased both NF-kappaB mRNA and protein nearly 7.5- and 4-fold, respectively. Expression of the NF-kappaB-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-alpha and NF-kappaB in vivo and suggest an important influence of TNF-alpha on postinjury IH.
Department of Surgery, University of Colorado Health Sciences Center, Denver 80262, USA.
Michael A
MA
Zimmerman
Craig H
CH
Selzman
Leonid L
LL
Reznikov
Stephanie A
SA
Miller
Christopher D
CD
Raeburn
Julie
J
Emmick
Xianzhong
X
Meng
Alden H
AH
Harken
D000818:Animals; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology; D020212:Carotid Artery Injuries / Q000150:complications / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D018932:Chemokine CCL2 / Q000378:metabolism; D004195:Disease Models, Animal; D006965:Hyperplasia / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D017539:Tunica Intima / Q000378:metabolism* / Q000473:pathology
D018932:Chemokine CCL2; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha