GSDME-mediated pyroptosis promotes the progression and associated inflammation of atherosclerosis.
Yuanyuan WeiBeidi LanTao ZhengLin YangXiaoxia ZhangLele ChengGulinigaer TuerhongjiangZuyi YuanYue YuPublished in: Nature communications (2023)
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.
Keyphrases
- low density lipoprotein
- high fat diet
- nlrp inflammasome
- cardiovascular disease
- oxidative stress
- inflammatory response
- cell death
- adipose tissue
- poor prognosis
- high fat diet induced
- insulin resistance
- endothelial cells
- single cell
- high glucose
- transcription factor
- gene expression
- cognitive decline
- type diabetes
- metabolic syndrome
- cell proliferation
- binding protein
- drug induced
- high throughput
- skeletal muscle
- heat stress
- wild type
- heat shock protein
- extracorporeal membrane oxygenation
- heat shock
- acute respiratory distress syndrome
- cell cycle arrest