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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Endothelial-specific deletion of Ets-1 attenuates Angiotensin II-induced cardiac fibrosis via suppression of endothelial-to-mesenchymal transition

  • Xu, Lian (State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Department of Hypertension, Ruijin Hospital and Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine) ;
  • Fu, Mengxia (State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Department of Hypertension, Ruijin Hospital and Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine) ;
  • Chen, Dongrui (State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Department of Hypertension, Ruijin Hospital and Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine) ;
  • Han, Weiqing (State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Department of Hypertension, Ruijin Hospital and Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine) ;
  • Ostrowski, Michael C. (Department of Cancer Biology and Genetics, The Comprehensive Cancer Center, Ohio State University) ;
  • Grossfeld, Paul (Division of Pediatric Cardiology, University of California San Diego School of Medicine) ;
  • Gao, Pingjin (State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Department of Hypertension, Ruijin Hospital and Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine) ;
  • Ye, Maoqing (State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Hypertension, Department of Hypertension, Ruijin Hospital and Shanghai Institute of Hypertension, Shanghai Jiao Tong University School of Medicine)
  • Received : 2018.09.07
  • Accepted : 2019.01.14
  • Published : 2019.10.31
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Abstract

Cardiac fibrosis is a common feature in chronic hypertension patients with advanced heart failure, and endothelial-to-mesenchymal transition (EndMT) is known to promote Angiotensin II (Ang II)-mediated cardiac fibrosis. Previous studies have suggested a potential role for the transcription factor, ETS-1, in Ang II-mediated cardiac remodeling, however the mechanism are not well defined. In this study, we found that mice with endothelial Ets-1 deletion showed reduced cardiac fibrosis and hypertrophy following Ang II infusion. The reduced cardiac fibrosis was accompanied by decreased expression of fibrotic matrix genes, reduced EndMT with decreased Snail, Slug, Twist, and ZEB1 expression, as well as reduced cardiac hypertrophy and expression of hypertrophy-associated genes was observed. In vitro studies using cultured H5V cells further confirmed that ETS-1 knockdown inhibited $TGF-{\beta}1$-induced EndMT. This study revealed that deletion of endothelial Ets-1 attenuated Ang II-induced cardiac fibrosis via inhibition of EndMT, indicating an important ETS-1 function in mediating EndMT. Inhibition of ETS-1 could be a potential therapeutic strategy for treatment of heart failure secondary to chronic hypertension.

Keywords

References

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