Gene deletion of NF-kappaB p105 enhances neointima formation in a mouse model of carotid artery injury.
The role of nuclear factor kappa-B (NF-kappaB) p105 for vascular inflammatory gene expression and neointima formation after arterial injury was studied. Mice carotid arteries were injured by ligation. Vascular NF-kappaB activation was monitored using a NF-kappaB luciferase reporter mouse. Mice with gene deletion of the NF-kappaB p105 subunit (p50 precursor) and the corresponding wild types were assessed for vascular gene expression and neointimal hyperplasia. NF-kappaB was activated in the injured vessel wall in wild type mice, and this was accompanied by increased expression of the proinflammatory genes tumor necrosis factor alpha, interleukin 1 beta, and inducible nitric oxide synthase. In contrast, NF-kappaB p105 knockout mice had reduced expression of the inflammatory genes and enhanced neointima formation four weeks after ligation. Basic fibroblast growth factor (bFGF) gene expression increased after arterial ligation. A higher percentage of bFGF positive cells were found in lesions from NF-kappaB p105 knock out mice. These data indicate that the p105 subunit of NF-kappaB plays an essential role in vascular healing, and defects in NF-kappaB p105 promote neointima hyperplasia.
Ruusalepp
Arno
A
Institute of Basic Medical Sciences, Department of Physiology, University of Oslo, Norway. Arno.Ruusalepp@kliinikum.ee
Yan
Zhong-Qun
ZQ
Carlsen
Harald
H
Czibik
Gabor
G
Hansson
Göran K
GK
Moskaug
Jan-Øyvind
JØ
Blomhoff
Rune
R
Valen
Guro
G
D000818:Animals; D020212:Carotid Artery Injuries / Q000503:physiopathology*; D004195:Disease Models, Animal; D024202:Electrophoretic Mobility Shift Assay; D017353:Gene Deletion; D015870:Gene Expression / Q000235:genetics; D007150:Immunohistochemistry; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D052002:NF-kappa B p50 Subunit / Q000235:genetics* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction / Q000379:methods; D011485:Protein Binding; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D017539:Tunica Intima / Q000378:metabolism* / Q000503:physiopathology; D014657:Vasculitis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology
D007375:Interleukin-1; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; C073701:Nfkb1 protein, mouse; D008156:Luciferases; D052247:Nitric Oxide Synthase Type II