The Nuclear Factor-kappa B p50 subunit is involved in flow-induced outward arterial remodeling.
OBJECTIVE
Outward arterial remodeling is a structural enlargement of the artery that is associated with unstable inflammatory atherosclerotic lesions. Toll-like receptor (Tlr) activation is known as a key pathway in outward arterial remodeling. Tlr activation results in nuclear translocation of the transcription factor Nuclear Factor-kappa B (NF-kappaB) that controls the transcription of many inflammatory genes. The NF-kappaB subunit p50 is generally considered to be an inhibitory subunit of the NF-kappaB complex. We therefore hypothesize that NF-kappaB p50 inhibits outward arterial remodeling.


RESULTS
Carotid artery ligation in mice, induced outward remodeling in contralateral arteries of NF-kappaB p50(-/-) (p50(-/-)) and wild type (WT) arteries. p50(-/-) arteries showed more outward arterial remodeling than WT arteries (19894.0+/-3136.7 microm(2) vs. 6120.7+/-2741.2 microm(2), respectively, P=0.006). In vitro, lipopolysaccharide induced higher cytokine expression levels in p50(-/-) cells compared to WT cells. In vivo, more outward remodeling in p50(-/-) arteries was associated with a decrease in collagen density and an increased influx of macrophages.


CONCLUSIONS
The NF-kappaB p50 subunit is involved in outward arterial remodeling. This is probably due to modulation of macrophage influx and adventitial collagen, leading to enhanced flow-induced outward arterial remodeling after targeted deletion of NF-kappaB subunit p50.
van Keulen
J Karlijn
JK
Department Experimental Cardiology, University Medical Center Utrecht, The Netherlands.
Timmers
Leo
L
van Kuijk
Liza P
LP
Retnam
Leslie
L
Hoefer
Imo E
IE
Pasterkamp
Gerard
G
Lim
Sai K
SK
de Kleijn
Dominique P V
DP
D000818:Animals; D002340:Carotid Artery Diseases / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology*; D002478:Cells, Cultured; D003094:Collagen / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology; D008264:Macrophages / Q000276:immunology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D052002:NF-kappa B p50 Subunit / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012039:Regional Blood Flow / Q000502:physiology*; D014657:Vasculitis / Q000276:immunology / Q000473:pathology / Q000503:physiopathology
D016207:Cytokines; D052002:NF-kappa B p50 Subunit; D012333:RNA, Messenger; D003094:Collagen; D020780:Matrix Metalloproteinase 9