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The protection effects of survivin in the cell model of CVB3-induced viral myocarditis

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Abstract

Viral myocarditis (VMC) is a widely studied but poorly understood inflammatory cardiomyopathy which mainly affects children and young adults and results in adverse outcomes. Cardiomyocyte apoptosis was reported important in the progress of coxsackievirus B3 (CVB3)-induced VMC and the blocking of this process may contribute to the therapeutic effect towards VMC. Therefore, this study was designed to explore whether survivin, one of the strongest antiapoptotic proteins, can protect cardiomyocytes from apoptosis in VMC and to discover its related mechanisms. Here, the cultured neonatal mouse cardiomyocytes (NMCs) were exposed to CVB3 to establish the cell model of VMC and the results of Western Blot showed that the protein expression of survivin in CVB3-infected NMCs varied at different post-infection time. Lentivirus was next used to examine the function of survivin in CVB3-infected NMCs. TUNEL assay demonstrated that the overexpression of survivin interrupted CVB3-induced apoptosis. It was next examined whether caspase-3 and -9 were involved in the antiapoptotic pathway initiated by survivin via Western Blot. The results showed a reverse relationship between the protein expression of survivin and that of cleaved caspase-3 and cleaved caspase-9, suggesting that survivin may attenuate apoptosis through restraining the activity of caspase-3 and -9. Moreover, the supernatant fluid of cultured NMCs was extracted to detect the quantitation of released lactate dehydrogenase (LDH) and a sharp decrease was discovered in the survivin-overexpressed group compared to the CVB3-infected group, indicating a protective role of survivin in the cell model of CVB3-induced myocarditis. This study demonstrated that survivin was triggered by CVB3 infection in NMCs and survivin executed its antiapoptotic effects via caspase-3- and caspase-9-dependent signaling pathway.

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Acknowledgements

This study was funded by the National Nature Science Foundation of China (Grant no. 81870275 and 81900346, China).

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Authors and Affiliations

  1. Department of Pediatric Cardiology, Children’s Hospital of Soochow University, Suzhou, 215025, China

    Rongzhou Wu & Haitao Lv

  2. Children’s Heart Center, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Institute of Cardiovascular Development and Translational Medicine, The Second School of Medicine, Wenzhou Medical University, Wenzhou, 325027, Zhejiang, China

    Rongzhou Wu, Tingting Wu, Ping Li, Qiaoyu Wang, Youyang Shi, Yi Zhan, Songyue Zhang, Tianhe Xia & Zhenquan Wang

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  1. Rongzhou Wu
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Wu, R., Wu, T., Li, P. et al. The protection effects of survivin in the cell model of CVB3-induced viral myocarditis. Heart Vessels 35, 1171–1179 (2020). https://doi.org/10.1007/s00380-020-01607-y

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