在动脉样硬化中通过STAT5信号驱动线粒体ROS泡细胞的形成
Laura Boccuni1,2, Frieda Marka1, Manuel Salzmann3
1Ludwig Boltzmann Institute for Cardiovascular Research, Vienna, Austria.
Science advances
|August 27, 2025
概括
氧化LDL (oxLDL) 通过增加线粒体超氧化物驱动泡细胞的形成. 这激活了STAT5,改变了新陈代谢,促进了动脉样硬化的进展. 抑制STAT5阻断了泡细胞的分化.
科学领域:
- 心血管生物学
- 细胞代谢
- 动脉样硬化研究
背景情况:
- 在动脉样硬化斑块的发展中,巨细胞转化为泡细胞至关重要.
- 氧化低密度脂蛋白 (oxLDL) 是泡细胞形成的关键驱动因素,影响巨细胞功能和新陈代谢.
研究的目的:
- 研究线粒体反应性氧物种 (ROS) 在oxLDL诱导的巨细胞变泡细胞分化中的作用.
- 阐明将线粒体ROS与泡细胞形成联系的分子机制.
主要方法:
- 使用细胞培养模型和体内研究 (老鼠和人类斑块).
- 研究了oxLDL对巨细胞代谢和STAT5信号的影响.
- 评估了STAT5抑制对泡细胞分化的影响.
主要成果:
- 巨细胞LDL衍生的超氧化物促进线粒体的新陈代谢编程,推动泡细胞的形成.
- 线粒体超氧化物激活STAT5,降低三碳酸循环活性并增强STAT5基因的可访问性.
- 在泡细胞中,STAT5信号是明显的特征,无论是ex vivo还是in vivo.
- 抑制STAT5可以防止成长为Trem2hiGpnmbhi泡细胞的分化.
结论:
- oxLDL诱导的线粒体超氧化激活STAT5,创建一个反循环,驱动巨细胞转化为泡细胞.
- 针对线粒体超氧化物-STAT5轴为动脉样硬化提供了潜在的治疗策略.
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