内皮细胞中的GSDME:通过线粒体损伤和STING通路激活诱导血管炎症和动脉样硬化
Shiyao Xie1,2,3, Enyong Su1,2,3, Xiaoyue Song1,2,3
1Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Biomedicines
|September 28, 2023
概括
加斯德明E (GSDME) 在动脉样硬化中驱动内皮炎症和斑块形成. 抑制GSDME可降低血管炎症和斑块发育,这表明它是一种治疗点.
科学领域:
- 心血管生物学 心血管生物学
- 炎症研究 炎症研究
- 分子医学是分子医学.
背景情况:
- 动脉样硬化斑块的启动包括内皮细胞炎症.
- 加斯德明E (GSDME) 参与热和炎症过程.
研究的目的:
- 调查GSDME在动脉样硬化开始中的作用.
- 为了阐明GSDME在动脉形成过程中的内皮细胞的下游机制.
主要方法:
- 在西方饮食中Gsdme-和阿波蛋白E缺乏 (ApoE) 的小鼠中的动脉样硬化模型.
- 在体外研究中,使用人静脉内皮细胞 (HUVEC) 暴露于氧化低密度脂蛋白 (ox-LDL).
- 利用干扰素基因 (STING) 途径激动剂来探索下游效应.
主要成果:
- 在ApoE小鼠动脉组织中观察到显著的GSDME激活,与动脉生成相关.
- 缺乏Gsdme的小鼠显示斑块形成减少和血管炎症.
- 抑制GSDME降低了ox-LDL诱导的内皮炎症,与线粒体损伤和细胞质dDNA增加有关.
- STING通路的激活在体内和体外部分抵消了GSDME抑制效应.
结论:
- 在动脉形成过程中,GSDME在内皮细胞炎症中发挥着关键作用.
- 在血管病理中,GSDME影响线粒体损伤和STING通路.
- 向GSDME为动脉样硬化和相关血管疾病提供了潜在的治疗策略.
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