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

作者：Duansak Naphatsanan; Schmid Scoenbein Geert W^*

来源：Microvascular Research, 2013, 90: 154-161.

DOI：10.1016/j.mvr.2013.09.003

Oxygen free radical and matrix metalloproteinases-9 (MMP-9) play an important pathophysiological role in the development of chronic hypertension. MMP-9 activities are regulated at different levels. We hypothesize that as mediators of the expression of MMP-9 the transcription factors like nuclear factor kappa B (NF-kappa B), c-fos and retinoic acid receptors-alpha (RAR-alpha) with binding sites to the MMP-9 promoter are overexpressed in the spontaneously hypertensive rat (SHR) in a process that is regulated by oxygen free radicals. Transcription factor NF-kappa B, c-fos and RAR-alpha expression levels were determined by immunohistochemistry in renal, cardiac and mesentery microcirculation of the SHR and its normotensive control, the Wistar Kyoto (WKY) rat. The animals were treated with a superoxide scavenger (Tempol) for eight weeks. The elevated plasma levels of thiobarbituric acid reactive substances and MMP-9 levels in the SHR were significantly decreased by Tempol treatment (P < 0.05). The NF-kappa B, c-fos and RAR-alpha expression levels in renal glomerular, heart and mesentery microvessels were enhanced in the SHR and could also be reduced by Tempol compared to untreated animals (P < 0.05). The enhanced MMP-9 levels in SHR microvessels co-express with transcription factors. These results suggest that elevated NF-kappa B, c-fos and RAR-a expressions and MMP-9 activity in the SHR are superoxide-dependent.

• 出版日期2013-11