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Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
08:43

Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation

Published on: May 31, 2016

Increased MMP-9 expression and activity by aortic smooth muscle cells after nitric oxide synthase inhibition is

Brian S Knipp1, Gorav Ailawadi, John W Ford

  • 1Jobst Vascular Research Laboratories, Section of Vascular Surgery, Ann Arbor, Michigan 48109-0329, USA. riversu@umich.edu

The Journal of Surgical Research
|January 21, 2004
PubMed
Abstract

Insights

Inhibiting inducible nitric oxide synthase (iNOS) in rat aortic smooth muscle cells increases matrix metalloproteinase 9 (MMP-9) expression and activity. This occurs via activation of nuclear factor-kappaB and activator protein-1 pathways, potentially leading to vessel wall damage.

Area of Science:

  • Vascular Biology
  • Molecular Medicine
  • Biochemistry

Background:

  • Inducible nitric oxide synthase (iNOS) plays a role in vascular homeostasis.
  • Matrix metalloproteinase 9 (MMP-9) is implicated in vascular remodeling and disease.
  • Understanding the interplay between iNOS and MMP-9 is crucial for cardiovascular research.

Purpose of the Study:

  • To elucidate the mechanism by which inhibiting iNOS in rat aortic smooth muscle cells (RA-SMC) leads to increased MMP-9 expression and activity.
  • To investigate the downstream signaling pathways involved in this process.

Main Methods:

  • Rat aortic smooth muscle cells (RA-SMC) were stimulated with interleukin-1beta.
  • iNOS was inhibited using aminoguanidine.
  • MMP-9 activity, protein, and mRNA levels were assessed using gelatin zymography, Western blot, and RT-PCR, respectively.
  • NF-kappaB and AP-1 activation were measured by electrophoretic mobility shift assay.

Main Results:

  • Aminoguanidine treatment significantly increased MMP-9 activity, pro-MMP-9 protein, and MMP-9 mRNA levels in stimulated RA-SMC.
  • Inhibition of iNOS led to decreased cytosolic IkappaB levels, indicating activation of the NF-kappaB pathway.
  • NF-kappaB and AP-1 binding activity were significantly increased following aminoguanidine administration.
  • No significant changes in MMP-2 or TIMP-1 were observed.

Conclusions:

  • iNOS inhibition in cytokine-stimulated RA-SMCs upregulates MMP-9 expression and activity.
  • This upregulation is associated with the activation of NF-kappaB and AP-1 signaling pathways.
  • Disruptions in iNOS function may promote MMP-9-mediated vascular damage through inflammatory cascades.

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