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The oxygen free radicals control MMP-9 and transcription factors expression in the spontaneously hypertensive rat

Naphatsanan Duansak1, Geert W Schmid-Schönbein

  • 1Department of Bioengineering, Institute of Engineering in Medicine, University of California, San Diego, La Jolla, CA 92093-0412, USA; Division of Physiology, Department of Preclinical Science, Faculty of Medicine, Thammasat University, Pathum Thani 12121, Thailand.

Microvascular Research
|September 25, 2013
PubMed

Insights

Oxygen free radicals contribute to chronic hypertension by increasing matrix metalloproteinases-9 (MMP-9) and overexpressing transcription factors like nuclear factor kappa B (NF-κB). Treatment with a superoxide scavenger reduced these effects in spontaneously hypertensive rats.

Area of Science:

  • Cardiovascular Research
  • Molecular Biology
  • Hypertension Pathophysiology

Background:

  • Oxygen free radicals and matrix metalloproteinases-9 (MMP-9) are implicated in chronic hypertension.
  • MMP-9 activity is tightly regulated, with transcription factors playing a key role.

Purpose of the Study:

  • To investigate the role of superoxide free radicals in regulating MMP-9 expression via transcription factors nuclear factor kappa B (NF-κB), c-fos, and retinoic acid receptors-α (RAR-α) in spontaneously hypertensive rats (SHR).

Main Methods:

  • Immunohistochemistry was used to determine the expression levels of NF-κB, c-fos, and RAR-α in the renal, cardiac, and mesenteric microcirculation of SHR and Wistar Kyoto (WKY) rats.
  • Animals were treated with the superoxide scavenger Tempol for eight weeks.
  • Plasma levels of thiobarbituric acid reactive substances and MMP-9 were measured.

Main Results:

  • Tempol treatment significantly reduced elevated plasma thiobarbituric acid reactive substances and MMP-9 levels in SHR.
  • Expression of NF-κB, c-fos, and RAR-α was enhanced in the microvessels of SHR and reduced by Tempol treatment.
  • Enhanced MMP-9 levels in SHR microvessels were found to co-express with these transcription factors.

Conclusions:

  • Elevated NF-κB, c-fos, and RAR-α expression and MMP-9 activity in spontaneously hypertensive rats are dependent on superoxide free radicals.
  • Targeting superoxide production may offer a therapeutic strategy for managing hypertension associated with these molecular pathways.

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