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Sestrin2 protects the myocardium against radiation-induced damage

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Abstract

The purpose of this study was to investigate the role of Sestrin2 in response to radiation-induced injury to the heart and on the cardiomyopathy development in the mouse. Mice with genetic deletion of the Sestrin2 (Sestrin2 knockout mice [Sestrin2 KO]) and treatment with irradiation (22 or 15 Gy) were used as independent approaches to determine the role of Sestrin2. Echocardiography (before and after isoproterenol challenge) and left ventricular (LV) catheterization were performed to evaluate changes in LV dimensions and function. Masson’s trichrome was used to assess myocardial fibrosis. Immunohistochemistry and Western blot were used to detect the capillary density. After 22 or 15 Gy irradiation, the LV ejection fraction (EF) was impaired in wt mice at 1 week and 4 months after irradiation when compared with sham irradiation. Compared to wt mice, Sestrin2 KO mice had significant reduction in reduced LVEF at 1 week and 4 months after irradiation. A significant increase in LV end-diastolic pressure and myocardial fibrosis and a significant decrease in capillary density were observed in irradiation-wt mice, as well as in irradiation-Sestrin2 KO mice. Sestrin2 involved in the regulation of cardiomyopathy (such as myocardial fibrosis) after irradiation. Overexpression of Sestrin2 might be useful in limiting radiation-induced myocardial injury.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 81201803).

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Authors and Affiliations

  1. Department of Medical Oncology, Cancer Center, Shengjing Hospital of China Medical University, 39 Huaxiang Road, Shenyang, 110022, China

    Yue-Can Zeng, Feng Chi, Rui Xing, Song Gao, Jia-Jia Chen, Qiong-Yu Duan, Yu-Nan Sun, Nan Niu, Mei-Yue Tang & Rong Wu

  2. Department of Radiation Oncology, University of Washington School of Medicine, Seattle, WA, USA

    Jing Zeng

  3. Department of Radiation Oncology, Nanfang Hospital of Southern Medical University, Guangzhou, 510515, China

    Hong-Mei Wang

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  1. Yue-Can Zeng
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  2. Feng Chi
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  3. Rui Xing
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  4. Jing Zeng
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  5. Song Gao
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  6. Jia-Jia Chen
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  7. Hong-Mei Wang
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  9. Yu-Nan Sun
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  10. Nan Niu
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  11. Mei-Yue Tang
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  12. Rong Wu
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Correspondence to Rong Wu.

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Zeng, YC., Chi, F., Xing, R. et al. Sestrin2 protects the myocardium against radiation-induced damage. Radiat Environ Biophys 55, 195–202 (2016). https://doi.org/10.1007/s00411-016-0643-8

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