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IL-17A promotes ventricular remodeling after myocardial infarction

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Abstract

Inflammatory responses play an important role in the pathogenesis of adverse ventricular remodeling after myocardial infarction (MI). We previously demonstrated that interleukin (IL)-17A plays a pathogenic role in myocardial ischemia/reperfusion injury and viral myocarditis. However, the role of IL-17A in post-MI remodeling and the related mechanisms have not been fully elucidated. Acute MI was induced by permanent ligation of the left anterior descending coronary artery in C57BL/6 mice. Repletion of IL-17A significantly aggravated both early- and late-phase ventricular remodeling, as demonstrated by increased infarct size, deteriorated cardiac function, increased myocardial fibrosis, and cardiomyocyte apoptosis. By contrast, genetic IL-17A deficiency had the opposite effect. Additional studies in vitro indicated that IL-17A induces neonatal cardiomyocyte (from C57BL/6 mice) apoptosis through the activation of p38, p53 phosphorylation, and Bax redistribution. These data demonstrate that IL-17A induces cardiomyocyte apoptosis through the p38 mitogen-activated protein kinase (MAPK)-p53-Bax signaling pathway and promotes both early- and late-phase post-MI ventricular remodeling. IL-17A might be an important target in preventing heart failure after MI.

Key message

• We demonstrated that IL-17A plays a pathogenic role both in the early and late stages of post-MI remodeling.

• IL-17A induces murine cardiomyocyte apoptosis.

• IL-17A induces murine cardiomyocyte apoptosis through the p38 MAPK-p53-Bax signaling pathway.

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Acknowledgments

This work was supported by grants from the National Basic Research Program of China (973 Program: 2013CB531103 and 2012CB517805), the National Natural Science Foundation of China (Nos. 91339118, 81222002, 81170303, and 81200177), and the Scientific and Technological Issues of Wuhan City (201161038341–03).

Conflict of interest

There is no potential conflict that exist.

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Authors and Affiliations

  1. Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, 430022, China

    Su-Feng Zhou, Jing Yuan, Meng-Yang Liao, Ni Xia, Ting-Ting Tang, Jing-Jing Li, Jiao Jiao, Wen-Yong Dong, Shao-Fang Nie, Zheng-Feng Zhu, Wen-Cai Zhang, Bing-Jie Lv, Yu-Hua Liao & Xiang Cheng

  2. Key Laboratory of Biological Targeted Therapy of the Ministry of Education, Wuhan, 430022, China

    Su-Feng Zhou, Jing Yuan, Meng-Yang Liao, Ni Xia, Ting-Ting Tang, Jing-Jing Li, Jiao Jiao, Wen-Yong Dong, Shao-Fang Nie, Zheng-Feng Zhu, Wen-Cai Zhang, Bing-Jie Lv, Yu-Hua Liao & Xiang Cheng

  3. The NO4 Hospital of Wuhan, Wuhan, 430000, China

    Hong Xiao

  4. Key Laboratory of Molecular Biophysics of the Ministry of Education, Cardio-X Institute, College of Life Science and Technology and Center of Human Genome Research, Huazhong University of Science and Technology, Wuhan, China

    Qing Wang & Xin Tu

  5. Center for Cardiovascular Genetics, Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA

    Qing Wang

  6. Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, 02115, USA

    Guo-Ping Shi

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  1. Su-Feng Zhou
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  18. Xiang Cheng
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Corresponding author

Correspondence to Xiang Cheng.

Additional information

Su-Feng Zhou, Jing Yuan, and Meng-Yang Liao contributed equally to this study.

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Cite this article

Zhou, SF., Yuan, J., Liao, MY. et al. IL-17A promotes ventricular remodeling after myocardial infarction. J Mol Med 92, 1105–1116 (2014). https://doi.org/10.1007/s00109-014-1176-8

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  • DOI: https://doi.org/10.1007/s00109-014-1176-8

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