Skip to main content
SpringerLink
Log in

Isoflurane Alleviates Myocardial Injury Induced by Hypoxia/Reoxygenation by Regulating miR-18a-5p

  • Published:
Cardiovascular Toxicology Aims and scope Submit manuscript

Abstract

The protective effect and mechanism of isoflurane on myocardial injury was investigated by constructing in vitro hypoxia/reoxygenation (HR) cell model. HR cell models were established in vitro and treated with isoflurane (ISO). qRT-PCR was used to detect the relative expression of miR-18a-5p. CCK-8 kit and flow cytometry were performed to evaluate cell proliferation and apoptosis. The myocardial injury related markers, such as Cκ-MB, cTnI and LDH were detected by ELISA. Luciferase reporter gene assay was used to verify the interaction between miR-18a-5p and target genes. The expression of miR-18a-5p was significantly increased in hypoxic cardiomyocytes compared with control group (P < 0.001). Meanwhile, cardiomyocytes in the HR group showed inhibition of proliferation, a significant increase in cell apoptosis and in myocardial injury indicators, such as Cκ-MB, cTnI and LDH (P < 0.001). However, 1% ISO treatment alleviated myocardial cell injury induced by HR. Transfection of miR-18a-5p under ISO reduced the protective effect of 1% ISO against myocardial cell damage. Luciferase report gene assay confirmed that CCND2 might be the target gene of miR-18a-5p. In the in vitro cell model of myocardium, ISO alleviated cardiomyocyte injury caused by hypoxia/reoxygenation by down-regulating the expression of miR-18a-5p.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Binder, A., Ali, A., Chawla, R., Aziz, H. A., Abbate, A., & Jovin, I. S. (2015). Myocardial protection from ischemia-reperfusion injury post coronary revascularization. Expert Review of Cardiovascular Therapy, 13, 1045–1057.

    Article  CAS  Google Scholar 

  2. Mokhtari-Zaer, A., Marefati, N., Atkin, S. L., Butler, A. E., & Sahebkar, A. (2018). The protective role of curcumin in myocardial ischemia-reperfusion injury. Journal of Cellular Physiology, 234, 214–222.

    Article  Google Scholar 

  3. Zorov, D. B., Juhaszova, M., & Sollott, S. J. (2014). Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiological Reviews, 94, 909–950.

    Article  CAS  Google Scholar 

  4. Ovize, M., Baxter, G. F., Di Lisa, F., Ferdinandy, P., Garcia-Dorado, D., Hausenloy, D. J., et al. (2010). Postconditioning and protection from reperfusion injury: Where do we stand? Position paper from the Working Group of Cellular Biology of the Heart of the European Society of Cardiology. Cardiovascular Research, 87, 406–423.

    Article  CAS  Google Scholar 

  5. Wojciechowska, A., Braniewska, A., & Kozar-Kaminska, K. (2017). MicroRNA in cardiovascular biology and disease. Advances in Clinical and Experimental Medicine, 26, 865–874.

    Article  Google Scholar 

  6. Hata, A. (2013). Functions of microRNAs in cardiovascular biology and disease. Annual Review of Physiology, 75, 69–93.

    Article  CAS  Google Scholar 

  7. Condorelli, G., Latronico, M. V., & Cavarretta, E. (2014). microRNAs in cardiovascular diseases: Current knowledge and the road ahead. Journal of the American College of Cardiology, 63, 2177–2187.

    Article  CAS  Google Scholar 

  8. Quiat, D., & Olson, E. N. (2013). MicroRNAs in cardiovascular disease: From pathogenesis to prevention and treatment. The Journal of Clinical Investigation, 123, 11–18.

    Article  CAS  Google Scholar 

  9. Liu, Y., Yang, L., Yin, J., Su, D., Pan, Z., Li, P., et al. (2018). MicroRNA-15b deteriorates hypoxia/reoxygenation-induced cardiomyocyte apoptosis by downregulating Bcl-2 and MAPK3. Journal of Investigative Medicine, 66, 39–45.

    Article  Google Scholar 

  10. Zhang, Y., & Chen, X. (2020). miR-18a-5p promotes proliferation and migration of vascular smooth muscle cells by activating the AKT/extracellular regulated protein kinases (ERK) signaling pathway. Medical Science Monitor, 26, e924625.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Lin, B., Feng, D., & Xu, J. (2019). Cardioprotective effects of microRNA-18a on acute myocardial infarction by promoting cardiomyocyte autophagy and suppressing cellular senescence via brain derived neurotrophic factor. Cell & Bioscience, 9, 38.

    Article  Google Scholar 

  12. Ferreira, R., Santos, T., Amar, A., Gong, A., Chen, T. C., Tahara, S. M., et al. (2014). Argonaute-2 promotes miR-18a entry in human brain endothelial cells. Journal of the American Heart Association, 3, e000968.

    Article  Google Scholar 

  13. Zhou, Y., Peng, D. D., Chong, H., Zheng, S. Q., Zhu, F., & Wang, G. (2019). Effect of isoflurane on myocardial ischemia-reperfusion injury through the p38 MAPK signaling pathway. European Review for Medical and Pharmacological Sciences, 23, 1342–1349.

    CAS  PubMed  Google Scholar 

  14. Pi, Z., Lin, H., & Yang, J. (2018). Isoflurane reduces pain and inhibits apoptosis of myocardial cells through the phosphoinositide 3-kinase/protein kinase B signaling pathway in mice during cardiac surgery. Molecular Medicine Reports, 17, 6497–6505.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Yang, L., Wu, J., Xie, P., Yu, J., Li, X., Wang, J., et al. (2019). Sevoflurane postconditioning alleviates hypoxia-reoxygenation injury of cardiomyocytes by promoting mitochondrial autophagy through the HIF-1/BNIP3 signaling pathway. PeerJ, 7, e7165.

    Article  Google Scholar 

  16. Yellon, D. M., & Hausenloy, D. J. (2007). Myocardial reperfusion injury. New England Journal of Medicine, 357, 1121–1135.

    Article  CAS  Google Scholar 

  17. Eltzschig, H. K., & Eckle, T. (2011). Ischemia and reperfusion–from mechanism to translation. Nature Medicine, 17, 1391–1401.

    Article  CAS  Google Scholar 

  18. Granger, D. N., & Kvietys, P. R. (2015). Reperfusion injury and reactive oxygen species: The evolution of a concept. Redox Biology, 6, 524–551.

    Article  CAS  Google Scholar 

  19. Law, C. H., Li, J. M., Chou, H. C., Chen, Y. H., & Chan, H. L. (2013). Hyaluronic acid-dependent protection in H9C2 cardiomyocytes: A cell model of heart ischemia-reperfusion injury and treatment. Toxicology, 303, 54–71.

    Article  CAS  Google Scholar 

  20. Tsutsumi, Y. M., Patel, H. H., Lai, N. C., Takahashi, T., Head, B. P., & Roth, D. M. (2006). Isoflurane produces sustained cardiac protection after ischemia-reperfusion injury in mice. Anesthesiology, 104, 495–502.

    Article  CAS  Google Scholar 

  21. Qiao, S., Olson, J. M., Paterson, M., Yan, Y., Zaja, I., Liu, Y., et al. (2015). MicroRNA-21 mediates isoflurane-induced cardioprotection against ischemia-reperfusion injury via Akt/Nitric oxide synthase/mitochondrial permeability transition pore pathway. Anesthesiology, 123, 786–798.

    Article  CAS  Google Scholar 

  22. Liu, H. J., & Liu, B. (2018). Inhibition of microRNA-23 contributes to the isoflurane-mediated cardioprotection against oxidative stress. Cardiovascular Toxicology, 18, 450–458.

    Article  CAS  Google Scholar 

  23. Wu, W., Zhou, X., Liu, P., Fei, W., Li, L., & Yun, H. (2014). Isoflurane reduces hypoxia/reoxygenation-induced apoptosis and mitochondrial permeability transition in rat primary cultured cardiocytes. BMC Anesthesiology, 14, 17.

    Article  Google Scholar 

  24. Lang, X. E., Wang, X., Zhang, K. R., Lv, J. Y., Jin, J. H., & Li, Q. S. (2013). Isoflurane preconditioning confers cardioprotection by activation of ALDH2. PLoS ONE, 8, e52469.

    Article  CAS  Google Scholar 

  25. Bauersachs, J., & Thum, T. (2011). Biogenesis and regulation of cardiovascular microRNAs. Circulation Research, 109, 334–347.

    Article  CAS  Google Scholar 

  26. Li, R., Yan, G., Li, Q., Sun, H., Hu, Y., Sun, J., et al. (2012). MicroRNA-145 protects cardiomyocytes against hydrogen peroxide (H(2)O(2))-induced apoptosis through targeting the mitochondria apoptotic pathway. PLoS ONE, 7, e44907.

    Article  CAS  Google Scholar 

  27. Ding, S., Liu, D., Wang, L., Wang, G., & Zhu, Y. (2020). Inhibiting microRNA-29a protects myocardial ischemia-reperfusion injury by targeting SIRT1 and suppressing oxidative stress and NLRP3-mediated pyroptosis pathway. Journal of Pharmacology and Experimental Therapeutics, 372, 128–135.

    Article  CAS  Google Scholar 

  28. Jiang, M., Yin, Y., Xie, L., & He, H. (2018). Plasma miR-18 screens acute myocardial infarction from healthy controls by targeting hypoxia inducible factor 1alpha. Clinical Laboratory, 64, 1207–1212.

    CAS  PubMed  Google Scholar 

  29. Cao, X., Wang, J., Wang, Z., Du, J., Yuan, X., Huang, W., et al. (2013). MicroRNA profiling during rat ventricular maturation: A role for miR-29a in regulating cardiomyocyte cell cycle re-entry. FEBS Letters, 587, 1548–1555.

    Article  CAS  Google Scholar 

  30. Zhu, W., Zhao, M., Mattapally, S., Chen, S., & Zhang, J. (2018). CCND2 overexpression enhances the regenerative potency of human induced pluripotent stem cell-derived cardiomyocytes: remuscularization of injured ventricle. Circulation Research, 122, 88–96.

    Article  CAS  Google Scholar 

Download references

Funding

This work was supported by the National Natural Science Foundation of China (No. 81801193).

Author information

Author notes

  1. Yujie Su and Guoqing Chen contributed equally to this study.

Authors and Affiliations

  1. Department of Anesthesiology, The First Hospital of Lanzhou University, No. 1, Donggang West Road, Lanzhou, 730000, China

    Yujie Su & Xiangmei Gao

  2. Anesthesia and Operation Centre, the First Medical Center, Chinese PLA General Hospital, Beijing, 100853, China

    Guoqing Chen & Faqiang Zhang

  3. School of Medicine, Nankai University, Tianjin, 300071, China

    Faqiang Zhang

  4. Department of Pain Medicine, The First Medical Center, Chinese PLA General Hospital, No. 51 Fucheng Road, Beijing, 100853, China

    Long Wang & Zeguo Feng

Authors
  1. Yujie Su
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Guoqing Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Faqiang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Long Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zeguo Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xiangmei Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

GQ Chen and FQ Zhang conducted most of the experiments and drafted the manuscript. L Wang and ZG Feng designed this study, edited the manuscript and made the revision. Yujie Su and Xiangmei Gao revised the manuscript according to the comments of reviewers. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Zeguo Feng or Xiangmei Gao.

Ethics declarations

Conflict of interest

The authors declare that there are no conflict of interests.

Additional information

Handling Editor: Rajiv Janardhanan.

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Su, Y., Chen, G., Zhang, F. et al. Isoflurane Alleviates Myocardial Injury Induced by Hypoxia/Reoxygenation by Regulating miR-18a-5p. Cardiovasc Toxicol 21, 800–807 (2021). https://doi.org/10.1007/s12012-021-09670-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12012-021-09670-1

Keywords

Search

Navigation