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GSDME-mediated pyroptosis promotes the progression and associated inflammation of atherosclerosis

Author

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  • Yuanyuan Wei

    (The First Affiliated Hospital of Xi’an Jiaotong University)

  • Beidi Lan

    (The First Affiliated Hospital of Xi’an Jiaotong University
    Ministry of Education, Xi’an Jiaotong University)

  • Tao Zheng

    (The First Affiliated Hospital of Xi’an Jiaotong University
    Ministry of Education, Xi’an Jiaotong University)

  • Lin Yang

    (Xi’an Jiaotong University)

  • Xiaoxia Zhang

    (Xi’an Jiaotong University)

  • Lele Cheng

    (The First Affiliated Hospital of Xi’an Jiaotong University
    Ministry of Education, Xi’an Jiaotong University)

  • Gulinigaer Tuerhongjiang

    (The First Affiliated Hospital of Xi’an Jiaotong University
    Ministry of Education, Xi’an Jiaotong University)

  • Zuyi Yuan

    (The First Affiliated Hospital of Xi’an Jiaotong University
    Ministry of Education, Xi’an Jiaotong University)

  • Yue Wu

    (The First Affiliated Hospital of Xi’an Jiaotong University
    Ministry of Education, Xi’an Jiaotong University)

Abstract

Pyroptosis, a type of Gasdermin-mediated cell death, contributes to an exacerbation of inflammation. To test the hypothesis that GSDME-mediated pyroptosis aggravates the progression of atherosclerosis, we generate ApoE and GSDME dual deficiency mice. As compared with the control mice, GSDME−/−/ApoE−/− mice show a reduction of atherosclerotic lesion area and inflammatory response when induced with a high-fat diet. Human atherosclerosis single-cell transcriptome analysis demonstrates that GSDME is mainly expressed in macrophages. In vitro, oxidized low-density lipoprotein (ox-LDL) induces GSDME expression and pyroptosis in macrophages. Mechanistically, ablation of GSDME in macrophages represses ox-LDL-induced inflammation and macrophage pyroptosis. Moreover, the signal transducer and activator of transcription 3 (STAT3) directly correlates with and positively regulates GSDME expression. This study explores the transcriptional mechanisms of GSDME during atherosclerosis development and indicates that GSDME-mediated pyroptosis in the progression of atherosclerosis could be a potential therapeutic approach for atherosclerosis.

Suggested Citation

  • Yuanyuan Wei & Beidi Lan & Tao Zheng & Lin Yang & Xiaoxia Zhang & Lele Cheng & Gulinigaer Tuerhongjiang & Zuyi Yuan & Yue Wu, 2023. "GSDME-mediated pyroptosis promotes the progression and associated inflammation of atherosclerosis," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36614-w
    DOI: 10.1038/s41467-023-36614-w
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