GSDME-mediated pyroptosis promotes the progression and associated inflammation of atherosclerosis.
GSDME-mediated pyroptosis promotes the progression and associated inflammation of atherosclerosis.
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DOI：
10.1038/s41467-023-36614-w
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发表时间：
2023-02-18
影响因子：
16.6
通讯作者：
Wu, Yue
中科院分区：
文献类型：
--
作者：
Wei, Yuanyuan;Lan, Beidi;Zheng, Tao;Yang, Lin;Zhang, Xiaoxia;Cheng, Lele;Tuerhongjiang, Gulinigaer;Yuan, Zuyi;Wu, Yue
Pyroptosis是一种由Gasdermin介导的细胞死亡，可导致炎症加重。为了验证GSDME介导的血小板减少加重动脉粥样硬化进展的假设，我们建立了ApoE和GSDME双重缺陷小鼠。与对照组小鼠相比，GSDME−/−/ApoE−/−小鼠在高脂饮食诱导下，动脉粥样硬化病变面积和炎症反应减少。人动脉粥样硬化单细胞转录组分析表明GSDME主要在巨噬细胞中表达。在体外，氧化低密度脂蛋白（ox-LDL）诱导巨噬细胞中GSDME的表达和细胞凋亡。从机制上讲，巨噬细胞中GSDME的消融抑制了ox-LDL诱导的炎症和巨噬细胞的焦下垂。此外，信号转导子和转录激活子3（STAT 3）直接与GSDME表达相关并正向调节GSDME表达。本研究探讨了GSDME在动脉粥样硬化发展过程中的转录机制，并表明GSDME介导的动脉粥样硬化进展中的细胞凋亡可能是动脉粥样硬化的潜在治疗方法。已显示巨噬细胞在动脉粥样硬化中具有重要功能。在这里，作者表明，在人类动脉粥样硬化斑块和小鼠模型中，GSDME和焦亡促进动脉粥样硬化，抑制这些途径可以减少与动脉粥样硬化疾病相关的病理学。
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. Macrophages have been shown to have an important function in atherosclerosis. Here the authors show that, in human atherosclerotic plaques and mouse models, GSDME and pyroptosis promote atherosclerosis and inhibition of these pathways could reduce pathology associated with atherosclerotic disease.
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影响因子：
8.7
作者：
Gordon S;Plüddemann A;Martinez Estrada F
通讯作者：
Martinez Estrada F
影响因子：
3.5
作者：
Lau, SK;Chu, PG;Weiss, LM
通讯作者：
Weiss, LM
影响因子：
5.2
作者：
de Beeck, Ken Op;Van Camp, Guy;Van Laer, Lut
通讯作者：
Van Laer, Lut
影响因子：
12.3
作者：
Ilicic T;Kim JK;Kolodziejczyk AA;Bagger FO;McCarthy DJ;Marioni JC;Teichmann SA
通讯作者：
Teichmann SA
DOI：
10.1093/bioinformatics/btp352
发表时间：
2009-08-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Li H;Handsaker B;Wysoker A;Fennell T;Ruan J;Homer N;Marth G;Abecasis G;Durbin R;1000 Genome Project Data Processing Subgroup
通讯作者：
1000 Genome Project Data Processing Subgroup