Lack of TNF-alpha attenuates intimal hyperplasia after mouse carotid artery injury. Am J Physiol Regul Integr Comp Physiol 2002 Aug;283(2):R505-12
Date
07/18/2002Pubmed ID
12121864DOI
10.1152/ajpregu.00033.2002Scopus ID
2-s2.0-0036333674 (requires institutional sign-in at Scopus site) 38 CitationsAbstract
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.
Author List
Zimmerman MA, Selzman CH, Reznikov LL, Miller SA, Raeburn CD, Emmick J, Meng X, Harken AHMESH terms used to index this publication - Major topics in bold
AnimalsCarotid Arteries
Carotid Artery Injuries
Chemokine CCL2
Disease Models, Animal
Hyperplasia
Immunohistochemistry
Male
Mice
Mice, Inbred Strains
Mice, Knockout
NF-kappa B
RNA, Messenger
Reverse Transcriptase Polymerase Chain Reaction
Tumor Necrosis Factor-alpha
Tunica Intima