凝血因子XI调节内皮细胞的透性和屏障功能在体外和体外
Cristina Puy1, Samantha A Moellmer1, Jiaqing Pang1
1Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR.
Blood
|August 19, 2024
概括
激活凝血因子XI (FXIa) 通过通过ADAM10通过裂解VE-cadherin增加了血管透性. 这条涉及VEGFR2和MAPK信号的途径为炎症性疾病提供了新的治疗点.
科学领域:
- 血管生物学 血管生物学
- 炎症研究 炎症研究
- 凝固级联是凝固级联的一个过程.
背景情况:
- 内皮屏障功能障碍是炎症性疾病的核心.
- 凝血因子XI (FXI) 影响炎症,但其在内皮屏障破坏中的作用尚不清楚.
研究的目的:
- 阐明FXIa破坏内皮屏障功能的机制.
- 研究FXIa在人类内皮细胞透性中的作用.
主要方法:
- 在HUVEC和HAEC中检查了VE-cadherin表达和裂变.
- 使用Transwell测试评估内皮细胞透性.
- 使用ADAM10抑制剂并分析VEGFR2和MAPK信号通路.
主要成果:
- 通过ADAM10激活,FXIa通过裂解VE-cadherin诱导内皮细胞的透性.
- 结合细胞表面受体的FXIa激活了VEGFR2,触发了MAPK通路并增加了活性ADAM10.
- 在败血症模型中,FXI抑制保留了屏障功能,并减少了可溶性VE-cadherin.
结论:
- FXIa通过通过ADAM10介导的VE-cadherin裂变来破坏内皮屏障功能.
- 这种新的FXIa-VEGFR2-MAPK-ADAM10通路有助于炎症中的血管透性.
- 抑制FXI激活可能会在炎症条件下保护内皮屏障功能.
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