Increased MMP-9 expression and activity by aortic smooth muscle cells after nitric oxide synthase inhibition is associated with increased nuclear factor-κB and activator protein-1 activity

Brian S. Knipp, Gorav Ailawadi, John W. Ford, David A. Peterson, Matthew J. Eagleton, Karen J. Roelofs, Kevin K. Hannawa, Michael P. Deogracias, Baoan Ji, Craig Logsdon, Kathleen D. Graziano, Diane M. Simeone, Robert W. Thompson, Peter K. Henke, James C. Stanley, Gilbert R. Upchurch

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Objective. To determine the mechanism underlying increased expression and activity of matrix metalloproteinase 9 (MMP-9) by rat aortic smooth muscle cells (RA-SMC) after inhibition of inducible nitric oxide synthase (iNOS). Methods and results. Treatment of interleukin-1β-stimulated RA-SMC with aminoguanidine led to an increase of 96% in MMP-9 activity (P = 0.003) by gelatin zymography, a 40% increase in pro-MMP-9 protein (P = 0.018) by Western blot, and a 155% increase in MMP-9 mRNA (P = 0.06) by reverse transcription polymerase chain reaction. Aminoguanidine also caused a 26% decrease in cytosolic IκB levels (P = 0.014) by Western blot, as well as a 97% increase in nuclear factor-κB binding and a 216% increase in activator protein-1 binding as measured by electrophoretic mobility shift assay. No significant changes were noted in MMP-2 or TIMP-1 expression, protein levels, or activity after aminoguanidine administration. Conclusion. MMP-9 expression and activity is increased in cytokine stimulated RA-SMCs after iNOS inhibition, coincident with activation of the nuclear factor-κB and activator protein-1 pathways. We speculate that local derangements in iNOS may favor MMP-9-dependent vessel wall damage in vivo via an inflammatory cascade mechanism.

Original languageEnglish (US)
Pages (from-to)70-80
Number of pages11
JournalJournal of Surgical Research
Volume116
Issue number1
DOIs
StatePublished - Jan 2004

Keywords

  • Aminoguanidine
  • Aortic smooth muscle cells
  • Inducible nitric oxidesynthase
  • Matrix metalloproteinase 9
  • Nuclear factor kappa β

ASJC Scopus subject areas

  • Surgery

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