Expression of a constitutive NF-kappa B-like activity is essential for proliferation of cultured bovine vascular smooth muscle cells

J Clin Invest. 1995 Nov;96(5):2521-7. doi: 10.1172/JCI118313.


We have recently discovered bovine and human vascular smooth muscle cells (SMCs) express a novel constitutive Nuclear Factor-kappa B (NF-kappa B)/Rel-like activity (Lawrence, R., L.-J. Chang, U. Siebenlist, P. Bressler, and G.E. Sonenshein. 1994. J. Biol. Chem. 269:28913-28918), here termed SMC-Rel. Since cytomegalovirus (CMV) infection of human vascular SMCs has been implicated in aberrant SMC proliferation during post-angioplasty restenosis, we tested the role of NF-kappa B/Rel activity in transactivation of the CMV immediate early (ie) promoter. The basal CMV ie promoter linked to three wild-type, but not mutant, copies of its NF-kappa B element was active in bovine aortic SMCs. The anti-oxidants N-acetyl cysteine (NAC) or pentoxifylline (PTX), which are used clinically to reduce NF-kappa B/Rel activity, inhibited NF-kappa B driven promoter transactivation, and SMC-Rel binding activity. Treatment with either NAC or PTX was observed to slow the growth of the SMCs in a dose dependent fashion. Microinjection of either purified I kappa B-alpha, a naturally occurring specific inhibitor of NF-kappa B/Rel activity, or double-stranded oligonucleotides harboring wild type, but not non-binding mutants of NF-kappa B elements selectively inhibited SMC proliferation. Thus constitutive NF-kappa B/Rel activity appears essential for proliferation of vascular SMCs and might be a novel target for therapeutic intervention for restenosis.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Cattle
  • Cell Division
  • Cells, Cultured
  • Cytomegalovirus / genetics*
  • Gene Expression Regulation, Viral
  • Molecular Sequence Data
  • Muscle, Smooth, Vascular / cytology*
  • Muscle, Smooth, Vascular / metabolism*
  • NF-kappa B / biosynthesis*
  • NF-kappa B / genetics
  • Promoter Regions, Genetic / genetics
  • Transfection


  • NF-kappa B