氧化LDL刺激PKM2介导的mtROS产生和细胞化
Jue Zhang1, Jackie Chang1, Vaya Chen1
1Versiti Blood Research Institute, Milwaukee, WI, USA.
Journal of lipid research
|April 18, 2025
概括
氧化低密度脂蛋白 (oxLDL) 通过增加巨细胞颗粒吸收来驱动动动脉硬化. 这一过程涉及CD36受体,线粒体活性氧物种 (mtROS) 和pyruvate kinase肌肉2 (PKM2) 信号传输.
科学领域:
- 心血管生物学 心血管生物学
- 细胞的新陈代谢
- 免疫学 免疫学 免疫学
背景情况:
- 氧化低密度脂蛋白 (oxLDL) 促进了益风性巨细胞表型,有助于动脉样硬化.
- 线粒体反应性氧物种 (mtROS) 与动脉样硬化有关,但它们的诱导机制和细胞效应尚不清楚.
- 巨细胞化对于恒温至关重要,但失调导致泡细胞的形成,这是动脉样硬化的标志.
研究的目的:
- 阐明oxLDL诱导mtROS产生和增强巨细胞细胞的机制.
- 为了确定参与巨细胞中oxLDL介导的细胞功能障碍的信号通路.
- 调查mtROS和特定信号分子在促进异位性巨细胞中细胞形成中的作用.
主要方法:
- 用oxLDL治疗了巨细胞,并评估了细胞活性.
- 使用Cd36-null巨细胞和siRNA敲除pyruvate kinase肌肉2 (PKM2) 来调查遗传贡献.
- 使用特定的抑制剂和淘汰技术分析了PKM2的线粒体转位.
- 在高脂肪和饮食中的易患动脉样硬化的Apoe-null小鼠被用于体内验证.
主要成果:
- 氧化低密度脂蛋白 (oxLDL) 显著增加了巨细胞的颗粒摄入量,这取决于CD36受体和mtROS生产.
- 在体内研究显示,高脂肪饮食中的动脉样硬化易患小鼠的大动脉泡性巨细胞中mtROS和细胞活性升高.
- 确定了一种新的途径,其中oxLDL/CD36相互作用促进了PKM2的线粒体转移,从而增加了mtROS和细胞化.
结论:
- 一个新的oxLDL-CD36-PKM2信号轴刺激了动性巨细胞中mtROS的产生和细胞化.
- 这一途径突出了一个关键的机制,它将脂质氧化,线粒体功能障碍和巨驱动动的动脉样硬化联系在一起.
- 准这种途径可能为动脉样硬化治疗提供治疗策略.
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