Open Access

Role of dysregulated ferroptosis‑related genes in cardiomyocyte ischemia‑reperfusion injury: Experimental verification and bioinformatics analysis

  • Authors:
    • Tie Hu
    • Wen-Peng Yu
    • Hua-Xi Zou
    • Zhi-Hao Chai
    • Shu-Yu Le
    • Fa-Jia Hu
    • Yi-Cheng Wang
    • Huang Huang
    • Song-Qing Lai
    • Ji-Chun Liu
  • View Affiliations

  • Published online on: September 28, 2023     https://doi.org/10.3892/etm.2023.12233
  • Article Number: 534
  • Copyright: © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Acute myocardial infarction is a life‑threatening condition with high mortality and complication rates. Although myocardial reperfusion can preserve ischemic myocardial tissue, it frequently exacerbates tissue injury, a phenomenon known as ischemia‑reperfusion injury (IRI). However, the underlying pathological mechanisms of IRI remain to be completely understood. Ferroptosis is a novel type of regulated cell death that is associated with various pathological conditions, including angiocardiopathy. The purpose of this article was to elucidate the possible mechanistic role of ferroptosis in IRI through bioinformatics analysis and experimental validation. Healthy and IRI heart samples were screened for differentially expressed ferroptosis‑related genes and functional enrichment analysis was performed to determine the potential crosstalk and pathways involved. A protein‑protein interaction network was established for IRI, and 10 hub genes that regulate ferroptosis, including HIF1A, EGFR, HMOX1, and ATF3 were identified. In vitro, an anoxia/reoxygenation (A/R) injury model was established using H9c2 cardiomyoblasts to validate the bioinformatics analysis results, and extensive ferroptosis was detected. A total of 4 key hub genes and 3 key miRNAs were also validated. It was found that IRI was related to the aberrant infiltration of immune cells and the small‑molecule drugs that may protect against IRI by preventing ferroptosis were identified. These results provide novel insights into the role of ferroptosis in IRI, which can help identify novel therapeutic targets.
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November-2023
Volume 26 Issue 5

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Hu T, Yu W, Zou H, Chai Z, Le S, Hu F, Wang Y, Huang H, Lai S, Liu J, Liu J, et al: Role of dysregulated ferroptosis‑related genes in cardiomyocyte ischemia‑reperfusion injury: Experimental verification and bioinformatics analysis. Exp Ther Med 26: 534, 2023
APA
Hu, T., Yu, W., Zou, H., Chai, Z., Le, S., Hu, F. ... Liu, J. (2023). Role of dysregulated ferroptosis‑related genes in cardiomyocyte ischemia‑reperfusion injury: Experimental verification and bioinformatics analysis. Experimental and Therapeutic Medicine, 26, 534. https://doi.org/10.3892/etm.2023.12233
MLA
Hu, T., Yu, W., Zou, H., Chai, Z., Le, S., Hu, F., Wang, Y., Huang, H., Lai, S., Liu, J."Role of dysregulated ferroptosis‑related genes in cardiomyocyte ischemia‑reperfusion injury: Experimental verification and bioinformatics analysis". Experimental and Therapeutic Medicine 26.5 (2023): 534.
Chicago
Hu, T., Yu, W., Zou, H., Chai, Z., Le, S., Hu, F., Wang, Y., Huang, H., Lai, S., Liu, J."Role of dysregulated ferroptosis‑related genes in cardiomyocyte ischemia‑reperfusion injury: Experimental verification and bioinformatics analysis". Experimental and Therapeutic Medicine 26, no. 5 (2023): 534. https://doi.org/10.3892/etm.2023.12233