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RETRACTED ARTICLE: Amphiregulin enhances cardiac fibrosis and aggravates cardiac dysfunction in mice with experimental myocardial infarction partly through activating EGFR-dependent pathway

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This article was retracted on 07 November 2022

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Abstract

Cardiac fibrosis (CF), a main process of ventricular remodeling after myocardial infarction (MI), plays a crucial role in the pathogenesis of heart failure (HF) post-MI. It is known that amphiregulin (AR) is involved in fibrosis of several organs. However, the expression of AR and its role post-MI are yet to be determined. This study aimed to investigate the impact of AR on CF post-MI and related mechanisms. Significantly upregulated AR expression was evidenced in the infarct border zone of MI mice in vivo and the AR secretion was enhanced in macrophages, but not in cardiac fibroblasts. In vitro, treatment with AR increased cardiac fibroblast migration, proliferation and collagen synthesis, and upregulated the expression of epidermal growth factor receptor (EGFR) and the downstream genes such as Akt, ERK1/2 and Samd2/3 on cardiac fibroblasts. All these effects could be abrogated by pretreatment with a specific EGFR inhibitor. To verify the functions of AR in MI hearts, lentivirus–AR–shRNA and negative control vectors were delivered into the infarct border zone. After 28 days, knock-down of AR increased the survival rate and improved cardiac function, while decreasing the extent of myocardial fibrosis of MI mice. Moreover, EGFR and the downstream genes were significantly downregulated in lentivirus–AR–shRNA treated MI mice. Our results thus indicate that AR plays an important role in promoting CF after MI partly though activating the EGFR pathway. Targeting AR might be a novel therapeutic option for attenuating CF and improve cardiac function after MI.

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Acknowledgements

This work was supported by the Nature Science Foundation of China Grant 81470470 and 81670321.

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  1. Liang Liu and Xian Jin contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, 600 Yishan Road, Shanghai, 200233, China

    Liang Liu, Xian Jin, Ya-Ping Zhang, Zhong’e Zhou, Rong Li & Cheng-Xing Shen

  2. Department of Ultrasound, the First Affiliated Hospital of Soochow University, Suzhou, China

    Cui-Fen Hu

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Liu, L., Jin, X., Hu, CF. et al. RETRACTED ARTICLE: Amphiregulin enhances cardiac fibrosis and aggravates cardiac dysfunction in mice with experimental myocardial infarction partly through activating EGFR-dependent pathway. Basic Res Cardiol 113, 12 (2018). https://doi.org/10.1007/s00395-018-0669-y

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