The Nuclear Factor-kappa B p50 subunit is involved in flow-induced outward arterial remodeling

Atherosclerosis. 2009 Feb;202(2):424-30. doi: 10.1016/j.atherosclerosis.2008.05.049. Epub 2008 Jun 5.


Aims: 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.

Methods and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carotid Artery Diseases / immunology
  • Carotid Artery Diseases / pathology*
  • Carotid Artery Diseases / physiopathology*
  • Cells, Cultured
  • Collagen / genetics
  • Collagen / metabolism
  • Cytokines / metabolism
  • Fibroblasts / cytology
  • Macrophages / immunology
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Mice, Inbred Strains
  • Mice, Mutant Strains
  • NF-kappa B p50 Subunit / genetics*
  • NF-kappa B p50 Subunit / metabolism*
  • RNA, Messenger / metabolism
  • Regional Blood Flow / physiology*
  • Vasculitis / immunology
  • Vasculitis / pathology
  • Vasculitis / physiopathology


  • Cytokines
  • NF-kappa B p50 Subunit
  • RNA, Messenger
  • Collagen
  • Matrix Metalloproteinase 9