Wang TL |
------>authors3_c= ------>paper_class1=1 ------>Impact_Factor=5.054 ------>paper_class3=2 ------>paper_class2=1 ------>vol=37 ------>confirm_bywho=None ------>insert_bywho=m001043 ------>Jurnal_Rank=10.3 ------>authors4_c= ------>comm_author= ------>patent_EDate=None ------>authors5_c= ------>publish_day=1 ------>paper_class2Letter=None ------>page2=794 ------>medlineContent= ------>unit=000 ------>insert_date=20091014 ------>iam=3 ------>update_date=None ------>author=?? ------>change_event=2 ------>ISSN= ------>authors_c= ------>score=500 ------>journal_name=J Mol Cell Cardiol ------>paper_name=Angiotensin II Signals Mechanical Stretch-Induced Cardiac Matrix Metalloproteinase Expression via JAK-STAT Pathway ------>confirm_date=None ------>tch_id=089173 ------>pmid=15350851 ------>page1=785 ------>fullAbstract=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. ------>tmu_sno=None ------>sno=22587 ------>authors2=Yang YH ------>authors3=Chang H ------>authors4=Hung CR ------>authors5= ------>authors6= ------>authors6_c= ------>authors=Wang TL ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c= ------>publish_area=0 ------>updateTitle=Angiotensin II signals mechanical stretch-induced cardiac matrix metalloproteinase expression via JAK-STAT pathway. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no=3 ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2004 ------>submit_flag=None ------>publish_month=9 |