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Follistatin-Like 1 Protects against Doxorubicin-Induced Cardiomyopathy through Upregulation of Nrf2

Doxorubicin- (DOX-) induced cardiomyocyte loss results in irreversible heart failure, which limits the clinical applications of DOX. Currently, there are no drugs that can effectively treat DOX-related cardiotoxicity. Follistatin-like 1 (FSTL1) has been reported to be a transforming growth factor-be...

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Published in:Oxidative medicine and cellular longevity 2020, Vol.2020 (2020), p.1-11
Main Authors: Liu, Yuan, Yang, Haibo, Zheng, Lu, Chen, Jun, Peng, Meng, Zhang, Wei, Sun, Jingjing, Zhao, Yintao, Zhang, Xiangqin
Format: Article
Language:English
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Summary:Doxorubicin- (DOX-) induced cardiomyocyte loss results in irreversible heart failure, which limits the clinical applications of DOX. Currently, there are no drugs that can effectively treat DOX-related cardiotoxicity. Follistatin-like 1 (FSTL1) has been reported to be a transforming growth factor-beta-inducible gene, and FSTL1 supplementation attenuated ischemic injury and cardiac apoptotic loss in mice. However, the effect of FSTL1 on DOX-induced cardiomyopathy has not been elucidated. We aimed to explore whether FSTL1 could prevent DOX-related cardiotoxicity in mice. Mice were intraperitoneally injected with a single dose of DOX to induce acute cardiotoxicity. We used an adeno-associated virus system to overexpress FSTL1 in the heart. DOX administration decreased FSTL1 mRNA and protein expression in the heart and in cells. FSTL1 prevented DOX-related cardiac injury and inhibited cardiac oxidative stress and apoptosis, thereby improving cardiac function in mice. FSTL1 also improved cardiomyocyte contractile functions in vitro. FSTL1 upregulated expression of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in DOX-treated hearts. FSTL1 was not capable of protecting against these toxic effects in Nrf2-deficient mice. In conclusion, FSTL1 protected against DOX-induced cardiotoxicity via upregulation of Nrf2 expression.
ISSN:1942-0900
1942-0994
DOI:10.1155/2020/3598715