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

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…

• TU
  Temple University
• NN
  National Natural Science Foundation of China

  Awards: 81822005, 2019YFA0802300, 92049203, 81941005, 81970351
• XJ
  Xi’an Jiaotong University

  Awards: 81941005, 92049203, 81822005