线粒体载荷质量决定了来自血管内皮细胞的细胞外囊泡的膜效应
Zahid A Manzar1, Lucas J Davis1, Karl F Swanson1
1Vascular Mechanobiology Laboratory, Department of Biomedical Engineering and Center for Cell, Gene, and Tissue Engineering, University at Buffalo-SUNY, Buffalo, NY 14260, USA.
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
|November 14, 2025
概括
来自内皮细胞 (EC) 的细胞外囊泡 (EV) 内的线粒体会影响心血管疾病 (CVD). 在EC-EV中改变的线粒体载荷促进炎症,这表明线粒体质量是心血管疾病的治疗点.
科学领域:
- 血管生物学 血管生物学
- 细胞生物学 细胞生物学
- 细胞外囊泡 细胞外囊泡
背景情况:
- 内皮细胞衍生的细胞外囊泡 (EC-EV) 中介细胞间通信.
- 较高的EC-EV水平与心血管疾病 (CVD) 有关.
- EC-EV的线粒体载荷可能会影响它们对目标内皮细胞 (EC) 的影响.
研究的目的:
- 调查线粒体载荷在EC-EV偏效应中的作用.
- 在EC-EV.中量化线粒体含量和质量.
- 确定线粒体载荷是否影响EC-EV对目标EC的影响.
主要方法:
- 从培养的人类EC.收集了大型细胞外囊泡 (EV).
- 量化了携带线粒体的EV (mitoEV),线粒体的载荷质量,以及线粒体的质量/极化.
- 激活EC与瘤坏死因子 (TNF) -α并与MitoTEMPO联合治疗.
- 在暴露于不同EV类型的目标EC中评估炎症基因表达.
- 使用光显微镜追踪EV线粒体货物转移.
主要成果:
- TNF-α激活增加了EV释放,包括具有较大,去极化线粒体载荷的mitoEV.
- 米托波治疗恢复了mitoEV的线粒体载荷质量和极化.
- 与C-EV不同的是,TNF-EV在目标EC上调节了炎症基因表达,与C-EV不同.
- EV线粒体载荷转移到目标EC线粒体并与其同居.
- 在EV中去极化线粒体载荷足以触发目标EC的炎症.
结论:
- 捐赠者EC线粒体的氧化还原状态调节 mitoEV线粒体的货物质量.
- 线粒体载荷质量影响它们诱导EC功能障碍和促进心血管疾病的能力.
- 在EC-mitoEV中,线粒体膜潜力 (ΔΨm) 可能成为血管医学中的新生物标志物和治疗标.
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