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

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 p...

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Autores principales: Hu, Tie, Yu, Wen-Peng, Zou, Hua-Xi, Chai, Zhi-Hao, Le, Shu-Yu, Hu, Fa-Jia, Wang, Yi-Cheng, Huang, Huang, Lai, Song-Qing, Liu, Ji-Chun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10587876/
https://www.ncbi.nlm.nih.gov/pubmed/37869642
http://dx.doi.org/10.3892/etm.2023.12233
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author Hu, Tie
Yu, Wen-Peng
Zou, Hua-Xi
Chai, Zhi-Hao
Le, Shu-Yu
Hu, Fa-Jia
Wang, Yi-Cheng
Huang, Huang
Lai, Song-Qing
Liu, Ji-Chun
author_facet Hu, Tie
Yu, Wen-Peng
Zou, Hua-Xi
Chai, Zhi-Hao
Le, Shu-Yu
Hu, Fa-Jia
Wang, Yi-Cheng
Huang, Huang
Lai, Song-Qing
Liu, Ji-Chun
author_sort Hu, Tie
collection PubMed
description 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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spelling pubmed-105878762023-10-21 Role of dysregulated ferroptosis‑related genes in cardiomyocyte ischemia‑reperfusion injury: Experimental verification and bioinformatics analysis Hu, Tie Yu, Wen-Peng Zou, Hua-Xi Chai, Zhi-Hao Le, Shu-Yu Hu, Fa-Jia Wang, Yi-Cheng Huang, Huang Lai, Song-Qing Liu, Ji-Chun Exp Ther Med Articles 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. D.A. Spandidos 2023-09-28 /pmc/articles/PMC10587876/ /pubmed/37869642 http://dx.doi.org/10.3892/etm.2023.12233 Text en Copyright: © Hu et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Hu, Tie
Yu, Wen-Peng
Zou, Hua-Xi
Chai, Zhi-Hao
Le, Shu-Yu
Hu, Fa-Jia
Wang, Yi-Cheng
Huang, Huang
Lai, Song-Qing
Liu, Ji-Chun
Role of dysregulated ferroptosis‑related genes in cardiomyocyte ischemia‑reperfusion injury: Experimental verification and bioinformatics analysis
title Role of dysregulated ferroptosis‑related genes in cardiomyocyte ischemia‑reperfusion injury: Experimental verification and bioinformatics analysis
title_full Role of dysregulated ferroptosis‑related genes in cardiomyocyte ischemia‑reperfusion injury: Experimental verification and bioinformatics analysis
title_fullStr Role of dysregulated ferroptosis‑related genes in cardiomyocyte ischemia‑reperfusion injury: Experimental verification and bioinformatics analysis
title_full_unstemmed Role of dysregulated ferroptosis‑related genes in cardiomyocyte ischemia‑reperfusion injury: Experimental verification and bioinformatics analysis
title_short Role of dysregulated ferroptosis‑related genes in cardiomyocyte ischemia‑reperfusion injury: Experimental verification and bioinformatics analysis
title_sort role of dysregulated ferroptosis‑related genes in cardiomyocyte ischemia‑reperfusion injury: experimental verification and bioinformatics analysis
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10587876/
https://www.ncbi.nlm.nih.gov/pubmed/37869642
http://dx.doi.org/10.3892/etm.2023.12233
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