大脑缺血导致内皮细胞中的全身Notch1活性驱动动动脉硬化
Mingming Liu1, Danni Wang1, Caiyun Qi1
1Department of Neurology, Tianjin Neurological Institute, Tianjin Institute of Immunology, State Key Laboratory of Experimental Hematology, International Joint Laboratory of Ocular Diseases, Ministry of Education, Haihe Laboratory of Cell Ecosystem, Laboratory of Post-Neuroinjury Neurorepair and Regeneration in Central Nervous System Tianjin & Ministry of Education, Tianjin Medical University General Hospital, Tianjin 300052, China.
Immunity
|July 30, 2024
概括
脑卒中引发了持续的内皮细胞激活和外周血管炎症,增加了复发性血管事件的风险. 针对Notch1信号提供了一个潜在的治疗策略,以防止与中风相关的动脉瘤进展.
科学领域:
- 心血管科学 心血管科学
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
背景情况:
- 脑卒中幸存者面临着由于持续的系统性动脉动脉进展而出现复发性血管事件的高风险.
- 内皮细胞 (EC) 激活是这一过程的关键驱动因素,但中风诱导持续EC变化的机制尚不清楚.
研究的目的:
- 调查中风是否会诱导外围内皮细胞的持续性亲炎性和亲atherogenic变化.
- 阐明潜在的分子机制,特别是Notch1信号传递的作用.
主要方法:
- 在小鼠模型中诱导脑缺血.
- 对外围内皮细胞激活,VCAM1表达,衰老和Notch1信号的分析.
- 骨髓细胞粘附和动脉动脉进展的评估.
- 干预ECs中的Notch1或VCAM1阻断抗体和遗传Notch1移除.
主要成果:
- 大脑缺血导致持续的内皮细胞激活,VCAM1上调和外周血管衰老,直至中风后4周.
- 这是由持续的Notch1信号传递的介导,由循环DLL1和Jagged1连接体的增加触发.
- 促炎和衰老的内皮促进了髓状细胞的粘附,加速了动脉动脉的进展.
- 抑制Notch1或VCAM1,或基因切除内皮Notch1,显著降低了动脉动脉进展.
结论:
- 脑卒中启动了一种全身机制,通过Notch1信号持续激活外围内皮细胞.
- 这种持续的内皮激活促进了动脉动脉的进展,并增加了复发性血管事件的风险.
- 准Notch1通路为预防中风后的二次血管并发症提供了一个有希望的治疗策略.
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