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

Tzong Luen Wang, Yu Hui Yang, Hang Chang, Chi Ren Hung

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

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 μM) 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 μM and 100 μM).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.

Original languageEnglish
Pages (from-to)785-794
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
Volume37
Issue number3
DOIs
Publication statusPublished - Sep 2004

Fingerprint

Matrix Metalloproteinase 14
Matrix Metalloproteinase 2
Matrix Metalloproteinases
Angiotensin II
Losartan
Cardiac Myocytes
Janus Kinase 2
Phosphatidylinositol 3-Kinase
Angiotensin Type 1 Receptor
Mechanical Stress
Angiotensin Receptor Antagonists
Mitogen-Activated Protein Kinase 1
Vacuum
Protein-Tyrosine Kinases
Protein Kinase C
Proteins
Messenger RNA
Membranes
alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide

Keywords

  • Angiotensin II
  • Cardiomyocytes
  • Janus kinase/STAT1
  • Matrix metalloproteinase
  • Mechanical stretch
  • Wistar rat

ASJC Scopus subject areas

  • Molecular Biology
  • Cardiology and Cardiovascular Medicine

Cite this

Angiotensin II signals mechanical stretch-induced cardiac matrix metalloproteinase expression via JAK-STAT pathway. / Wang, Tzong Luen; Yang, Yu Hui; Chang, Hang; Hung, Chi Ren.

In: Journal of Molecular and Cellular Cardiology, Vol. 37, No. 3, 09.2004, p. 785-794.

Research output: Contribution to journalArticle

Wang, Tzong Luen ; Yang, Yu Hui ; Chang, Hang ; Hung, Chi Ren. / Angiotensin II signals mechanical stretch-induced cardiac matrix metalloproteinase expression via JAK-STAT pathway. In: Journal of Molecular and Cellular Cardiology. 2004 ; Vol. 37, No. 3. pp. 785-794.
@article{804cd8d9128a4522a59f752950338cb3,
title = "Angiotensin II signals mechanical stretch-induced cardiac matrix metalloproteinase expression via JAK-STAT pathway",
abstract = "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 μM) 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 μM and 100 μM).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.",
keywords = "Angiotensin II, Cardiomyocytes, Janus kinase/STAT1, Matrix metalloproteinase, Mechanical stretch, Wistar rat",
author = "Wang, {Tzong Luen} and Yang, {Yu Hui} and Hang Chang and Hung, {Chi Ren}",
year = "2004",
month = "9",
doi = "10.1016/j.yjmcc.2004.06.016",
language = "English",
volume = "37",
pages = "785--794",
journal = "Journal of Molecular and Cellular Cardiology",
issn = "0022-2828",
publisher = "Academic Press Inc.",
number = "3",

}

TY - JOUR

T1 - Angiotensin II signals mechanical stretch-induced cardiac matrix metalloproteinase expression via JAK-STAT pathway

AU - Wang, Tzong Luen

AU - Yang, Yu Hui

AU - Chang, Hang

AU - Hung, Chi Ren

PY - 2004/9

Y1 - 2004/9

N2 - 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 μM) 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 μM and 100 μM).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.

AB - 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 μM) 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 μM and 100 μM).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.

KW - Angiotensin II

KW - Cardiomyocytes

KW - Janus kinase/STAT1

KW - Matrix metalloproteinase

KW - Mechanical stretch

KW - Wistar rat

UR - http://www.scopus.com/inward/record.url?scp=4444370733&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4444370733&partnerID=8YFLogxK

U2 - 10.1016/j.yjmcc.2004.06.016

DO - 10.1016/j.yjmcc.2004.06.016

M3 - Article

C2 - 15350851

AN - SCOPUS:4444370733

VL - 37

SP - 785

EP - 794

JO - Journal of Molecular and Cellular Cardiology

JF - Journal of Molecular and Cellular Cardiology

SN - 0022-2828

IS - 3

ER -