GSDME-mediated pyroptosis promotes the progression and associated inflammation of atherosclerosis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 36807553.
- Also identified by DOI 10.1038/s41467-023-36614-w and PMC identifier 9938904.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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<sup>-/-</sup>/ApoE<sup>-/-</sup> 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.
Medical subject headings
- Pyroptosis
- Atherosclerosis