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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, RESULTS. Meshes: Animals, Aorta, Cells, Cultured, Cytosol, Guanidines, Male, Matrix Metalloproteinase 2, Matrix Metalloproteinase 3, Myocytes, Smooth Muscle, NF-kappa B, Nitric Oxide Synthase, Nitric Oxide Synthase Type II, Protein Precursors, RNA, Messenger, Rats, Rats, Sprague-Dawley, Tissue Inhibitor of Metalloproteinases, Transcription Factor AP-1.
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Is increased MMP-9 expression and activity by aortic smooth muscle cells after nitric oxide synthase inhibition associated with increased nuclear factor-kappaB and activator protein-1 activity? Context: To determine the mechanism underlying increased expression and activity of matrix metalloproteinase 9 (MMP-9) by rat aortic smooth muscle cells (RA-SMC) after inhibition of inducible nitric oxide synthase (iNOS). Treatment of interleukin-1beta-stimulated RA-SMC with aminoguanidine led to an increase of 96% in MMP-9 activity (P = 0.003) by gelatin zymography, a 40% increase in pro-MMP-9 protein (P = 0.018) by Western blot, and a 155% increase in MMP-9 mRNA (P = 0.06) by reverse transcription polymerase chain reaction. Aminoguanidine also caused a 26% decrease in cytosolic IkappaB levels (P = 0.014) by Western blot, as well as a 97% increase in nuclear factor-kappaB binding and a 216% increase in activator protein-1 binding as measured by electrophoretic mobility shift assay. No significant changes were noted in MMP-2 or TIMP-1 expression, protein levels, or activity after aminoguanidine administration.
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MMP-9 expression and activity is increased in cytokine stimulated RA-SMCs after iNOS inhibition, coincident with activation of the nuclear factor-kappaB and activator protein-1 pathways. We speculate that local derangements in iNOS may favor MMP-9-dependent vessel wall damage in vivo via an inflammatory cascade mechanism. Final Decision: yes