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Exosomes from myoblasts induced by hypoxic preconditioning improved ventricular conduction by increasing Cx43 expression in hypothermia ischemia reperfusion hearts

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Abstract

Myocardial ischemia–reperfusion arrhythmia after cardiac surgery is common and seriously affects quality of life. Remote ischemic preconditioning can reduce the myocardial damage caused by severe ischemia. However, the underlying mechanism is not well understood. This study aimed to investigate the effects of exosomes derived from C2C12 mouse myoblasts after hypoxic preconditioning (HP) on ventricular conduction in hypothermic ischemia–reperfusion hearts. Myocardial ischemia–reperfusion model rats were established using the Langendorff cardiac perfusion system. Exosomes derived from normoxic (ExoA) and hypoxia-preconditioned (ExoB) C2C12 cells were injected into the jugular vein of the model rats. The time to heartbeat restoration, arrhythmia type and duration, and heart rate were recorded after myocardial ischemia–reperfusion. Conduction velocity on the surface of left ventricle was measured using a microelectrode array after 30 min of balanced perfusion, 15 min of reperfusion, and 30 min of reperfusion. Immunohistochemistry and western blotting were performed to determine the distribution and relative expression of connexin 43 (Cx43). ExoB contained more exosomes than ExoA, showing that HP stimulated the release of exosomes. The IR + ExoB group showed faster recovery of ventricular myocardial activity, a lower arrhythmia score, faster conduction velocity, and better electrical conductivity than the IR group. ExoB increased the expression of Cx43 and reduced its lateralization in the ventricular muscle. Our study showed that exosomes induced by hypoxic preconditioning can improve ventricular myocardial conduction and reperfusion arrhythmia in isolated hearts after hypothermic ischemia–reperfusion.

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Data availability

The datasets used and/or analyzed in this study are available from the corresponding authors upon reasonable request.

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Acknowledgements

We thank Jianman Wang (M.D.College of Basic Medical College, Guizhou Medical University, Guiyang, Guizhou, China), Sihui Lu (M.D.College of Anesthesiology, Guizhou Medical University, Guiyang, Guizhou, China) and Anqiang Zhou (M.D.College of Clinic, Guizhou Medical University, Guiyang, Guizhou, China) for their kindful assistance with this study.

Funding

This study was supported by the Science and Technology Fund of the Guizhou Provincial Health Commission (Grant No. Gzwkj2021-270; Gzwkj2022-131).

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Author notes

  1. Tingju Hu and Rui Duan have contributed equally to this work.

Authors and Affiliations

  1. Suzhou Medical College of Soochow University, Suzhou, 215123, Jiangsu, China

    Tingju Hu

  2. College of Anesthesiology, Guizhou Medical University, Guiyang, 550004, Guizhou, China

    Tingju Hu, Hong Gao, Xue Bai, Xiang Huang, Xu Yan, Li An, Yanyan Ma, Rui Chen & Mi Gan

  3. Department of Anesthesiology, Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, Guizhou, China

    Tingju Hu & Li An

  4. Translational Medicine Research Center, Guizhou Medical University, Guiyang, 550001, Guizhou, China

    Tingju Hu & Rui Chen

  5. Department of Pain, The Second People’s Hospital of Guiyang, Guiyang, 550081, Guizhou, China

    Rui Duan & Sen Hong

  6. Department of Anesthesiology, Affiliated Hospital of Guizhou Medical University, 28 Guiyi Street, Guiyang, 550004, Guizhou, China

    Hong Gao

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Contributions

Tingju Hu and Rui Duan conducted experiments, collected data, and wrote the manuscript; Hong Gao was responsible for project conceptualization and design, and manuscript proofreading; Xue Bai, Xiang Huang, Rui Chen, Li An, Xu Yan, Yanyan Ma, Sen Hong, and Mi Gan conducted the experiments. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Hong Gao.

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All authors declare no conflict of interest.

Ethical approval

This study was approved by the Ethics Committee of Guizhou Medical University (Approval number: 2200390). All animal handling and experiments were conducted in accordance with the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. The rats were provided by the Animal Experimental Center of Guizhou Medical University [license no. : SCXK (Qian) 2018-0001]. The rats were housed under a 12 h light-dark cycle and were given free access to food and water.

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Hu, T., Duan, R., Gao, H. et al. Exosomes from myoblasts induced by hypoxic preconditioning improved ventricular conduction by increasing Cx43 expression in hypothermia ischemia reperfusion hearts. Cytotechnology (2024). https://doi.org/10.1007/s10616-024-00634-1

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