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Molecular Medicine Reports
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Print ISSN: 1791-2997 Online ISSN: 1791-3004
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September-2026 Volume 34 Issue 3

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Article Open Access

PCSK9 alleviates doxorubicin‑induced pyroptosis of cardiomyocytes

  • Authors:
    • Chaochu Cui
    • Jinyu Zhao
    • Xiaoqian Li
    • Shengming Huang
    • Gang Liu
    • Xinhui Xu
    • Can Guo
    • Tiesuo Zhao
    • Jiang Du
    • Shipeng Li
    • Xianwei Wang
    • Jianbo Yang

  • View Affiliations / Copyright

    Affiliations: Henan Key Laboratory of Medical Tissue Regeneration, Henan Medical University, Xinxiang, Henan 453003, P.R. China, Department of Immunology, School of Basic Medical Sciences, Henan Medical University, Xinxiang, Henan 453000, P.R. China, Henan Joint International Research Laboratory of Stem Cell Medicine, School of Medical Engineering, Henan Medical University, Xinxiang, Henan 453003, P.R. China, Teaching Laboratory of Medical Imaging Technology, School of Life Sciences and Technology, Henan Medical University, Xinxiang, Henan 453003, P.R. China
    Copyright: © Cui et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 255
    |
    Published online on: July 14, 2026
       https://doi.org/10.3892/mmr.2026.13965
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Abstract

Prolonged survival of patients with cancer has increased the need to address chemotherapy‑related cardiovascular complications. Doxorubicin (DOX), a widely used anthracycline, is associated with dose‑dependent cardiotoxicity, known as DOX‑induced cardiotoxicity (DIC), which limits its clinical utility. DOX triggers cardiomyocyte pyroptosis via the NLRP3/caspase‑1/gasdermin D pathway, a potential underlying mechanism of DIC. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a key regulator of lipid metabolism and inflammation, has been implicated in NLRP3 inflammasome activation and the progression of cardiovascular diseases; however, its role in DIC remains unclear. The present study demonstrated that DOX downregulates PCSK9 expression in cardiomyocytes in a dose‑dependent manner. Through proteomic analysis and PCSK9 knockout cell and mouse models, it was found that the deletion of PCSK9 exacerbated DOX‑induced pyroptosis and cardiac dysfunction. These results revealed the protective effect of PCSK9 in DOX‑mediated cardiotoxicity and indicated that PCSK9 regulation may provide a new cardioprotective strategy for patients receiving anthracycline chemotherapy.

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Copy and paste a formatted citation
Spandidos Publications style
Cui C, Zhao J, Li X, Huang S, Liu G, Xu X, Guo C, Zhao T, Du J, Li S, Li S, et al: PCSK9 alleviates doxorubicin‑induced pyroptosis of cardiomyocytes. Mol Med Rep 34: 255, 2026.
APA
Cui, C., Zhao, J., Li, X., Huang, S., Liu, G., Xu, X. ... Yang, J. (2026). PCSK9 alleviates doxorubicin‑induced pyroptosis of cardiomyocytes. Molecular Medicine Reports, 34, 255. https://doi.org/10.3892/mmr.2026.13965
MLA
Cui, C., Zhao, J., Li, X., Huang, S., Liu, G., Xu, X., Guo, C., Zhao, T., Du, J., Li, S., Wang, X., Yang, J."PCSK9 alleviates doxorubicin‑induced pyroptosis of cardiomyocytes". Molecular Medicine Reports 34.3 (2026): 255.
Chicago
Cui, C., Zhao, J., Li, X., Huang, S., Liu, G., Xu, X., Guo, C., Zhao, T., Du, J., Li, S., Wang, X., Yang, J."PCSK9 alleviates doxorubicin‑induced pyroptosis of cardiomyocytes". Molecular Medicine Reports 34, no. 3 (2026): 255. https://doi.org/10.3892/mmr.2026.13965
Copy and paste a formatted citation
x
Spandidos Publications style
Cui C, Zhao J, Li X, Huang S, Liu G, Xu X, Guo C, Zhao T, Du J, Li S, Li S, et al: PCSK9 alleviates doxorubicin‑induced pyroptosis of cardiomyocytes. Mol Med Rep 34: 255, 2026.
APA
Cui, C., Zhao, J., Li, X., Huang, S., Liu, G., Xu, X. ... Yang, J. (2026). PCSK9 alleviates doxorubicin‑induced pyroptosis of cardiomyocytes. Molecular Medicine Reports, 34, 255. https://doi.org/10.3892/mmr.2026.13965
MLA
Cui, C., Zhao, J., Li, X., Huang, S., Liu, G., Xu, X., Guo, C., Zhao, T., Du, J., Li, S., Wang, X., Yang, J."PCSK9 alleviates doxorubicin‑induced pyroptosis of cardiomyocytes". Molecular Medicine Reports 34.3 (2026): 255.
Chicago
Cui, C., Zhao, J., Li, X., Huang, S., Liu, G., Xu, X., Guo, C., Zhao, T., Du, J., Li, S., Wang, X., Yang, J."PCSK9 alleviates doxorubicin‑induced pyroptosis of cardiomyocytes". Molecular Medicine Reports 34, no. 3 (2026): 255. https://doi.org/10.3892/mmr.2026.13965
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