Angiotensin II downregulates ACE2-mediated enhancement of MMP-2 activity in human cardiofibroblasts

Tang Ching Kuan, Mu Yuan Chen, Yan Chiou Liao, Li Ko, Yi Han Hong, Chun Yi Yen, Wen Yeh Hsieh, Kun Shan Cheng, Chien Liang Wu, Chih-Sheng Lin*

*Corresponding author for this work

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Angiotensin converting enzyme II (ACE2) is a component of the renin-angiotensin system (RAS) that negatively regulates angiotensin II (Ang II). Ang II, in turn, affects the expression of matrix metalloproteinases (MMPs) to induce heart remodeling. The specific mechanisms by which ACE2 regulates MMP-2, however, remain unclear. The aim of this study was to investigate the regulatory relationships between Ang II, ACE2, and MMP-2. ACE2 expression was upregulated and downregulated in human cardiofibroblasts (HCFs) by lentiviral infection. Effects on MMP-2 activity, shed ACE2 activity, extracellular signal-regulated kinase (ERK) signaling pathway, and ADAM metallopeptidase domain 17 (ADAM17) expression were assessed. ACE2 increased MMP-2 activity, and Ang II inhibited this effect through the Ang II type-1 receptor (AT1R) and ERK1/2 signaling pathway. Ang II also reduced the effect of ACE2 on ERK1/2 levels, the activity of shed ACE2, and adam17 expression in HCFs. Additionally, these Ang II-mediated reductions could be attenuated by AT1R antagonist valsartan. In conclusion, these data help to clarify how ACE2 and Ang II interact to regulate MMP-2 and control tissue remodeling in heart disease.

Original languageEnglish
Pages (from-to)435-442
Number of pages8
JournalBiochemistry and Cell Biology
Volume91
Issue number6
DOIs
StatePublished - 1 Dec 2013

Keywords

  • angiotensin II
  • angiotensin-converting enzyme II
  • human cardiofibroblasts
  • matrix metalloproteinases- 2

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    Kuan, T. C., Chen, M. Y., Liao, Y. C., Ko, L., Hong, Y. H., Yen, C. Y., Hsieh, W. Y., Cheng, K. S., Wu, C. L., & Lin, C-S. (2013). Angiotensin II downregulates ACE2-mediated enhancement of MMP-2 activity in human cardiofibroblasts. Biochemistry and Cell Biology, 91(6), 435-442. https://doi.org/10.1139/bcb-2013-0031