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Nuclear factor‐ kappa B expression and matrix metalloproteinase activity in hypertension
Author(s) -
Wu KwanI,
SchmidSchönbein Geert W.
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.592.1
Subject(s) - pyrrolidine dithiocarbamate , endocrinology , medicine , kidney , matrix metalloproteinase , transcription factor , inflammation , nf κb , hypothalamus , immunohistochemistry , renal cortex , chemistry , biochemistry , gene
Our recent evidences suggest that inflammation of the spontaneously hypertensive rat (SHR) is associated with an uncontrolled matrix metalloproteinase (MMP) activity. We hypothesize that the transcription factor NF‐κB is overexpressed in the SHR and involved in the overexpression of MMPs. NF‐κB expression level and translocation were compared between Wistar Kyoto rat and SHR kidney, heart, and brain. In addition, the animals were treated with a NF‐κB inhibitor, pyrrolidine dithiocarbamate (PDTC), for ten weeks. To determine the correlation between NF‐κB and MMP, MMP‐2 and −9 activities were examined after treatment. Immunohistochemistry showed that NF‐κB expression is significantly increased in SHR in renal glomerular and tubulointerstitial areas and brain hypothalamus compared to that in WKY (p<0.05), but not in myocardium and cerebral cortex. Significant NF‐κB translocation into the nucleus was found in renal tubular cells, cardiac muscle cells, and arterioles of kidney and brain in SHR. After PDTC treatment, the systolic blood pressure in SHR was suppressed by 36 % as compared to no significant difference in WKY rats. NF‐κB expression level in treated‐SHR was also decreased in renal glomerular and tubulointerstitial areas and hypothalamus compared to non‐treated animals (p <0.05). Furthermore, MMP‐2 activity was significantly reduced by PDTC treatment in both WKY and SHR. The enhanced MMP‐9 activity in SHR was also significantly decreased by PDTC (p <0.01). These results suggest NF‐κB is an important transcription factor in the SHR and may be responsible for its enhanced MMP activity. Supported by HL 10881