The nitric oxide donor DETA-NONOate decreases matrix metalloproteinase-9 expression and activity in rat aortic smooth muscle and abdominal aortic explants.

Abstract

Our objective was to examine the role of an exogenous nitric oxide (NO) donor, DETA-NONOate (DETA), on matrix metalloproteinase (MMP)-9, MMP-2, and tissue inhibitor of matrix metalloproteinases (TIMP)-1 expression and activity in interleukin (IL)-1beta-induced rat aortic smooth muscle cells (RA-SMCs) and rat aortic explants (RAEs). RA-SMCs were incubated with IL-1beta (2 ng/ml), an inflammatory cytokine known to induce MMP-9 expression, and increasing concentrations of DETA (0, 1.0, 10, 100 microM; n = 3/group) for 48 hr. RAEs were incubated with IL-1beta (2 ng/mL) and increasing concentrations of DETA (0, 5.0, 50, 100, and 500 microM; n = 3/group) for 48 hr. Media were collected and assayed for NO(x) by the Griess reaction and MMP-9 activity by zymography. Messenger RNA (mRNA) was extracted from cells and analyzed for MMP-9, MMP-2, and TIMP-1 expression levels by quantitative real-time reverse-transcriptase polymerase chain reaction. All statistical analyses were performed by analysis of variance. In RA-SMCs and RAEs, DETA administration resulted in a dose-dependent increase in media NOx concentration (RA-SCM p < 0.01, RAE p < 0.01) and a concurrent decrease in both MMP-9 expression (RASMC p = 0.01, RAE p = 0.01) and activity (RASMC p = 0.04, RAE p = 0.006). There were no significant differences seen in MMP-2 and TIMP-1 expression or activity in response to DETA exposure. DETA decreased IL-1beta-induced MMP-9 expression and activity in both RA-SMCs and RAEs in a dose-dependent fashion. In addition, DETA administration had no effect on MMP-2 or TIMP-1 expression or activity in vitro. These data suggest that NO donors may be beneficial in decreasing MMP-9 levels and might serve to inhibit MMP-9-dependent vessel wall remodeling seen during abdominal aortic aneurysm formation.

• Authors: Indranil Sinha, Kevin K Hannawa, Gorav Ailawadi, Derek T Woodrum, John W Ford, Peter K Henke, James C Stanley, Matthew J Eagleton, Gilbert R Upchurch Jr
• Journal: Annals of vascular surgery (Ann Vasc Surg) Vol. 20 Issue 1 Pg. 92-8 (Jan 2006) ISSN: 0890-5096 [Print] Netherlands
• PMID: 16378139 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Nitric Oxide Donors
• Nitroso Compounds
• RNA, Messenger
• 2,2'-(hydroxynitrosohydrazono)bis-ethanamine
• Matrix Metalloproteinase 9

Topics

• Animals
• Aorta, Abdominal
• Cells, Cultured
• Dose-Response Relationship, Drug
• Down-Regulation
• Male
• Matrix Metalloproteinase 9 (biosynthesis, genetics, metabolism)
• Muscle, Smooth, Vascular
• Nitric Oxide Donors (pharmacology)
• Nitroso Compounds (pharmacology)
• RNA, Messenger (analysis, isolation & purification)
• Rats
• Rats, Sprague-Dawley