通过VEGFR2-CBL-NF-κB信号传递,FAK活动会加剧扰乱的流媒体动脉硬化
James M Murphy1, Duyen Thi Kieu Tran1, Kyuho Jeong2
1Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
The Journal of biological chemistry
|June 16, 2025
概括
血液流动受到干扰会通过内皮细胞 (EC) 激活引发血管炎症. 这项研究表明,抑制焦粘附激酶 (FAK) 可能减少EC炎症,为动脉样硬化提供潜在的治疗策略.
科学领域:
- 心血管生物学 心血管生物学
- 内皮细胞信号传递
- 动脉样硬化病原体的产生
背景情况:
- 动脉样硬化发生在血液流动受损的部位,导致血管炎症.
- 干扰的流量增加了内皮细胞 (EC) 透性和炎症基因表达.
- 血管内皮生长因子受体2 (VEGFR2) 参与流动诱导的EC炎症,但其精确的信号通路尚不清楚.
研究的目的:
- 阐明在流介导性内皮炎中将焦点粘附激酶 (FAK) 和VEGFR2连接起来的信号机制.
- 研究FAK-VEGFR2相互作用在动脉样硬化发展的背景下所起的作用.
主要方法:
- 在内皮细胞中研究了FAK和NF-kB的流媒体激活.
- 在流动条件下检查了FAK,VEGFR2和卡西塔斯B系淋巴瘤 (CBL) 之间的相互作用.
- 用西方饮食的Apoe-/-小鼠来评估FAK活性在主动脉的阿瑟罗区.
主要成果:
- 对于FAK和NF-kB的流介导激活,VEGFR2的VEGF原始化是至关重要的.
- FAK激活促进CBL的氨酸酸化,CBL在流动下与VEGFR2相互作用.
- FAK抑制减少了VEGFR2-FAK-CBL复合体的形成和VEGFR2细胞膜表达.
- Apoe-/-小鼠在扰乱的流域中显示出增加的FAK活性,与细胞表面VEGFR2.2升高相关.
结论:
- FAK激活是干扰流动诱导的内皮炎症的关键调解者.
- 在这种炎症信号通路中,FAK-VEGFR2-CBL轴起着重要的作用.
- 抑制FAK活性可能是减少动脉样硬化中的内皮前炎性反应的治疗标.
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