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The Protective Mechanism of Dexmedetomidine in Regulating Atg14L-Beclin1-Vps34 Complex Against Myocardial Ischemia-Reperfusion Injury

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Abstract

The blood flow restoration of ischemic tissues causes myocardial injury. Dexmedetomidine (Dex) protects multi-organs against ischemia/reperfusion (I/R) injury. This study investigated the protective mechanism of Dex post-treatment in myocardial I/R injury. The rat model of myocardial I/R was established. The effects of Dex post-treatment on cardiac function and autophagy flow were observed. Dex attenuated myocardial I/R injury and reduced I/R-induced autophagy in rats. Dex weakened the interactions between Beclin1 and Vps34 and Beclin1 and Atg14L, thus downregulating Vps34 kinase activity. In vitro, the cardiomyocytes subjected to oxygen glucose deprivation/reoxygenation were treated with Dex and PI3K inhibitor LY294002. LY294002 attenuated the myocardial protective effect of DEX, indicating that Dex protected against cardiac I/R by activating the PI3K/Akt pathway. In conclusion, Dex upregulated the phosphorylation of Beclin1 at S295 site by activating the PI3K/Akt pathway and reduced the interactions of Atg14L-Beclin1-Vps34 complex, thus inhibiting autophagy and protecting against myocardial I/R injury.

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Data Availability

The analyzed data sets generated during the study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, No.1 Jianshe East Road, Zhengzhou, 450000, China

    Yanna Li, Mingcui Qu, Fei Xing, Huixin Li, Dan Cheng, Na Xing & Wei Zhang

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  1. Yanna Li
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  2. Mingcui Qu
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  4. Huixin Li
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  5. Dan Cheng
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  6. Na Xing
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  7. Wei Zhang
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Contributions

Conceptualization: YL and MQ; validation, research, resources, data reviewing, and writing: FX, HL, and DC; review and editing: NX and WZ. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Na Xing or Wei Zhang.

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Ethics Approval and Consent to Participate

This study got the permission of the Ethical Committee of the First Affiliated Hospital of Zhengzhou University. All the animal experiments were implemented on the guide for the care and use of laboratory animals.

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Not applicable.

Competing Interests

The authors declare no competing interests.

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Associate Editor Nicola Smart oversaw the review of this article

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Li, Y., Qu, M., Xing, F. et al. The Protective Mechanism of Dexmedetomidine in Regulating Atg14L-Beclin1-Vps34 Complex Against Myocardial Ischemia-Reperfusion Injury. J. of Cardiovasc. Trans. Res. 14, 1063–1074 (2021). https://doi.org/10.1007/s12265-021-10125-9

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  • DOI: https://doi.org/10.1007/s12265-021-10125-9

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