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Resveratrol ameliorates myocardial ischemia/reperfusion induced necroptosis through inhibition of the Hippo pathway

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Abstract

Myocardial ischemia-reperfusion (I/R) injury is a major cause of poor hemodynamic reconstitution outcomes after myocardial infarction or circulatory arrest. Currently, the search for effective therapeutic agents and tools is a focus of research in the field of myocardial I/R injury. Resveratrol (Res) has been extensively studied in recent years because of its good cardiovascular therapeutic effects, but its specific mechanism of action has not been fully elucidated. Therefore, the aim of this study was to investigate the mechanism of interaction between myocardial I/R injury and Res in vitro and in vivo. In our in vivo study, we used PI/TUNEL staining and western blotting to detect relevant necroptotic key molecules such as RIP1, RIP3 and p-MLKL/MLKL to observe myocardial necroptosis. The extent of myocardial injury was determined using hematoxylin and eosin (HE) staining and 2,3,5-triphenyltetrazolium chloride (TTC) staining as well as serum levels of CK-MB and LDH and echocardiography. In the in vitro study, cellular injury was assessed by CCK-8 and cell supernatant LDH levels. In addition, we used small interfering RNA (siRNA) transfection to knock down YAP, a key effector molecule of the Hippo pathway, to validate the molecular mechanism of action by which Res exerts myocardial protection. The localization of YAP in H9c2 cardiomyocytes was examined using immunofluorescence. Our data demonstrated that Res could ameliorate myocardial I/R-induced necroptosis by modulating the Hippo pathway, and that the beneficial effect of Res might be associated with nuclear translocation of the transcriptional regulator YAP.

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Data Availability

The data that support the findings of this study are available from the corresponding author or first author (tianhao2020@aliyun.com) upon appropriate request.

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Acknowledgements

This study was supported by grants from the National Natural Science Foundation of China (No. 81970722).

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Authors and Affiliations

  1. Department of Anesthesiology, Renmin Hospital of Wuhan University, 430060, Wuhan, Hubei Province, China

    Hao Tian, Yonghong Xiong & Zhongyuan Xia

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  1. Hao Tian
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  2. Yonghong Xiong
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  3. Zhongyuan Xia
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Contributions

Hao Tian contributed to the conception and design of the experiment, and participated in data acquisition. Yonghong Xiong contributed to the data analysis and interpretation. Zhongyuan Xia the guarantor of this work. All authors approved the final version of the paper.

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Correspondence to Zhongyuan Xia.

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Tian, H., Xiong, Y. & Xia, Z. Resveratrol ameliorates myocardial ischemia/reperfusion induced necroptosis through inhibition of the Hippo pathway. J Bioenerg Biomembr 55, 59–69 (2023). https://doi.org/10.1007/s10863-022-09954-3

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  • DOI: https://doi.org/10.1007/s10863-022-09954-3

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