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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

07/18/2002

Pubmed ID

12121864

DOI

10.1152/ajpregu.00033.2002

Scopus ID

2-s2.0-0036333674   33 Citations

Abstract

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 AH

Author

Michael A. Zimmerman MD, FACS Professor in the Surgery department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Carotid 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
jenkins-FCD Prod-486 e3098984f26de787f5ecab75090d0a28e7f4f7c0