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PIM3 regulates myocardial ischemia/reperfusion injury via ferroptosis

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Abstract

Background

Myocardial ischemia/reperfusion (I/R) injury is closely related with cardiovascular diseases; however, the underlying pathogenic mechanisms remain not fully understood. This study sought to investigate the effect and mechanisms of PIM3 implicated in myocardial I/R injury using a rat model of myocardial I/R injury and a cell model of oxygen–glucose deprivation/reoxygenation (OGD/R) induction.

Methods

The morphology changes were detected by HE staining while cell viability was accessed by the CCK-8 method. The characteristics of ferroptosis were evaluated by ROS production, MDA content, SOD level, iron content, TfR1, FTH1, and GPX4 expression.

Results

Myocardial I/R operation increased myocardial tissue damage in rats, while OGD/R treatment reduced the viability of H9c2 cells. Both myocardial I/R operation and OGD/R stimulation increased ferroptosis, as demonstrated by elevated ROS, MDA, iron content, decreased SOD level, upregulation of TfR1, and downregulation of FTH1 and GPX4. Additionally, myocardial I/R modeling or OGD/R treatment enhanced the expression of PIM3. Silencing of PIM3 inhibited ferroptosis, which resulted in alleviated myocardial I/R-induced damage and improved H9c2 cell survival.

Conclusions

Our findings highlight a vital role of PIM3 in myocardial I/R injury, indicating that PIM3-targeting ferroptosis may be a promising target for the development of novel therapies of myocardial I/R injury-associated diseases.

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Data availability

The data are available from the corresponding author on reasonable request.

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Funding

This research was supported by the Hunan Provincial Health and Family Planning Commission Project (20180200), Hunan Provincial Science and Technology Department Project (2020SK51824), Hunan Provincial Education Department Project (21B0416), Hunan Provincial Health Commission (B202301047951).

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, The First Affiliated Hosptal, University of South China, Hengyang, 421001, Hunan, People’s Republic of China

    Ting Li, Ying Tan, Yutao Peng & Xuefeng Xu

  2. Department of Cardiovascular Medicine, The Second Affiliated Hosptal, University of South China, Hengyang, 421001, Hunan, People’s Republic of China

    Fangyao Liu

  3. School of Resource, Environment and Safety Engineering, Univerity of South China, Hengyang, 421001, Hunan, People’s Republic of China

    Yushan Yang

Authors
  1. Ting Li
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  2. Fangyao Liu
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  3. Ying Tan
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  4. Yutao Peng
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  5. Xuefeng Xu
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Contributions

(I) Conception and design: Ting Li and Yushan Yang; (II) Administrative support: Xuefeng Xu; (III) Collection and assembly of data: Fangyao Liu and Ying Tan; (IV) Data analysis and interpretation: Yutao Peng (V) Manuscript writing: All authors; The authors declare that all data were generated in-house and that no paper mill was used.

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Correspondence to Yushan Yang.

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The authors have no relevant financial or non-financial interests to disclose.

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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Animal Care Committee of University of South China.

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Li, T., Liu, F., Tan, Y. et al. PIM3 regulates myocardial ischemia/reperfusion injury via ferroptosis. Genes Genom 46, 161–170 (2024). https://doi.org/10.1007/s13258-023-01475-6

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  • DOI: https://doi.org/10.1007/s13258-023-01475-6

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