在存在因子VIII和/或埃米齐祖马布的情况下,在血管细胞上生成血栓
Sénadé Atsou1, Célia Schellenberg2, Jeremy Lagrange2
1Université Paris-Saclay, INSERM, Hémostase Inflammation Thrombose HITh U1176, 94276, Le KremLin-Bicêtre, France.
Journal of thrombosis and haemostasis : JTH
|September 30, 2023
概括
第八因子 (FVIII) 和埃米齐祖马布增强了动脉细胞上的血栓生成. 然而,刺激的内皮细胞限制了这种效果,而艾米齐祖马布与APCC一起导致了过度的血栓生成.
科学领域:
- 血液静止和血栓形成
- 血管生物学 血管生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 血生成试验通常使用合成脂.
- 这项研究研究了人类动脉细胞上的血栓生成:大动脉内皮细胞 (hAEC) 和血管光滑肌细胞 (hVSMC).
研究的目的:
- 评估休息和刺激HAECs和hVSMCs的能力,以支持因子VIII (FVIII) 或埃米齐祖马布介导的血栓生成.
- 描述这些动脉细胞的促凝和抗凝性质.
主要方法:
- 对hVSMCs和 hAECs的组织因子 (TF),脂素 (PS) 暴露,TFPI和血栓模块素的分析.
- 化细胞与含有FVIII,埃米齐祖马布,活性蛋白质复合物缩物 (APCC) 或组合的FVIII缺乏血.
主要成果:
- hVSMCs和 hAECs表达TF和PS; hAECs还表达血栓模块素和TFPI,这表明hVSMCs具有前凝性质.
- 在两种细胞类型上,FVIII和埃米齐祖马布促进了血栓生成,在hVSMCs上更为如此.
- 刺激的 hAECs 显示由于抗凝固因子增加而减少了FVIII/emicizumab驱动的血栓生成,而 emicizumab 与APCC导致了过度的血栓生成.
结论:
- 瘤亡因子刺激HAECs增加了前凝和抗凝因子.
- 刺激HAECs中增强的抗凝剂活性限制了FVIII和埃米齐祖马布的疗效.
- 当艾米齐祖马布与APCC结合使用时,可以克服这种限制,从而导致过度的血栓生成.
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