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Depletion of microRNA-92a Enhances the Role of Sevoflurane Treatment in Reducing Myocardial Ischemia–Reperfusion Injury by Upregulating KLF4

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Abstract

Objective

As some articles have highlighted the role of microRNA-92a (miR-92a) in myocardial ischemia–reperfusion injury (MI/RI), this article aimed to investigate the effect of miR-92a on Sevoflurane (Sevo)-treated MI/RI via regulation of Krüppel-like factor 4 (KLF4).

Methods

An MI/RI rat model was established by ligating the left anterior descending coronary artery. The cardiac function, pathological changes of myocardial tissues, inflammatory response, oxidative stress and cardiomyocyte apoptosis in MI/RI rats were determined. KLF4 and miR-92a expression was detected in the myocardial tissue of rats, and the target relationship between miR-92a and KLF4 was confirmed.

Results

Sevo treatment alleviated myocardial damage, inflammatory response, oxidative stress response, and cardiomyocyte apoptosis, and improved cardiac function in MI/RI rats. miR-92a increased and KLF4 decreased in the myocardial tissue of MI/RI rats. KLF4 was targeted by miR-92a. Downregulation of miR-92a or upregulation of KLF4 further enhanced the effect of Sevo treatment on MI/RI.

Conclusion

This study suggests that depletion of miR-92a promotes upregulation of KLF4 to improve cardiac function, reduce cardiomyocyte apoptosis and further enhance the role of Sevo treatment in alleviating MI/RI.

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Data Availability

The original contributions presented in the study are included in the article/Supplementary Material, and further inquiries can be directed to the corresponding author.

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Acknowledgements

We would like to give our sincere gratitude to the reviewers for their constructive comments.

Funding

This work was supported by Shanghai University of Traditional Chinese Medicine budget project (18LK055); the Special Project of Integrated Traditional Chinese and Western Medicine in general hospital of Shanghai Health Committee (Grant Number ZHYY-ZXYJHZX-202023).

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Authors and Affiliations

  1. Department of Geriatrics, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200071, China

    Qianfu Wu, Haihui Wang, Rong Lu & Guoliang Yan

  2. Department of Pathology, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, No. 1200, Cailun, Pudong New Area, Shanghai, 201203, China

    Qianfu Wu, Jiali Zheng, Panwei Hu, Rong Lu & Guoliang Yan

  3. Department of Cardiology, Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, Anhui, China

    Fei He

  4. Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China

    Hongjing Zhang

  5. Department of Nuclear Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, 200030, Shanghai, China

    Chang Cheng

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  1. Qianfu Wu
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Contributions

Rong Lu and Guoliang Yan designed the study; Qianfu Wu, Fei He, Jiali Zheng and Hongjing Zhang conducted experimental studies; Haihui Wang, Chang Cheng and Panwei Hu performed data analysis; Qianfu Wu and Haihui Wang edited the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Rong Lu.

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Ethics Statement

All animal experiments were in compliance with the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The protocol was approved by the Committee on the Ethics of Animal Experiments of School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine.

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Patients signed informed consent regarding publishing their data and photographs.

Conflict of Interest

The authors have no conflicts of interest to declare that are relevant to the content of this article.

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Qianfu Wu and Haihui Wang are co-first authors.

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Wu, Q., Wang, H., He, F. et al. Depletion of microRNA-92a Enhances the Role of Sevoflurane Treatment in Reducing Myocardial Ischemia–Reperfusion Injury by Upregulating KLF4. Cardiovasc Drugs Ther 37, 1053–1064 (2023). https://doi.org/10.1007/s10557-021-07303-x

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