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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Angiotensin II signals mechanical stretch-induced cardiac matrix metalloproteinase expression via JAK-STAT pathway.

BACKGROUND: Mechanical stress induces many pathophysiological effects in cardiomyocytes. The objective of this study was to test the hypothesis that angiotensin II is a potential mediator of stretch-induced activation of matrix metalloproteinases (MMP). METHODS: Neonatal rat cardiomyocytes grown on a flexible membrane were cyclically stretched achieving up to 20% elongation at 60 cycles/min (using a vacuum). We explored the signaling pathways involved in cyclical stretch-induced expression of MMP-14 and MMP-2. RESULTS: Cyclical mechanical stretch significantly increased mRNA expression and protein synthesis for MMP-14 and MMP-2 from the 6(th) to 24(th) h. The increase in MMP-14 and -2 proteins after stretch was completely blocked after the pretreatment with losartan (an angiotensin II AT1 receptor antagonist, 200 nM) and AG-490 (a Janus kinase 2 tyrosine kinase inhibitor, 100 nM) but not with PD 98059 (an inhibitor of p42/ p44 mitogen-activated protein kinase, 50 microM) or wortmannin (a phosphatidylinositol 3-kinase, 30 nM). By zymography, MMP-2 activity was increased by cyclical stretch that was significantly attenuated by losartan and AG-490. The mechanical strain also increased the immunohistochemical labeling of MMP-14 and -2 that was attenuated by adding losartan. Cyclical stretch increased the expression of STAT-1 that was abolished by pretreating with losartan or AG-490 (50 microM and 100 microM). CONCLUSION: These findings indicate that cyclical stretch induces MMP-14 and -2 expression in neonatal rat cardiomyocytes and that the induction is mediated by the angiotensin II-JAK-STAT1 pathway.[1]

References

  1. Angiotensin II signals mechanical stretch-induced cardiac matrix metalloproteinase expression via JAK-STAT pathway. Wang, T.L., Yang, Y.H., Chang, H., Hung, C.R. J. Mol. Cell. Cardiol. (2004) [Pubmed]
 
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