Model-dependent contributions of FXII and FXI to venous thrombosis in mice.
Model-dependent contributions of FXII and FXI to venous thrombosis in mice.
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DOI：
10.1111/jth.15037
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发表时间：
2020-11
期刊：
影响因子：
--
通讯作者：
Mackman N
中科院分区：
文献类型：
--
作者：
Grover SP;Olson TM;Cooley BC;Mackman N
在动物模型中，内源性途径因子（F）XII和FXI已被证明有助于血栓形成。我们在三种不同的小鼠模型中评估了FXII和FXI在静脉血栓形成中的作用。在FXII或FXI遗传缺陷的小鼠中评估静脉血栓形成。采用三种模型：下腔静脉（IVC）淤滞模型、IVC狭窄模型和股静脉电解损伤模型。在IVC停滞模型中，FXII和FXI缺乏不影响血栓的大小，但它们的缺乏与纤维蛋白（原）水平降低和中性粒细胞胞外陷阱标记物瓜氨酸化组蛋白H3水平升高相关。相比之下，在IVC狭窄模型中，FXII或FXI缺乏导致血栓重量和血栓形成发生率显著和等效降低。与IVC停滞模型中形成的血栓相比，IVC狭窄模型中形成的血栓含有显著更高水平的瓜氨酸化组蛋白H3。FXII或FXI的缺失也导致股静脉电解损伤模型中纤维蛋白和血小板蓄积的显著和等效减少。总的来说，这些数据表明，FXII和FXI对停滞模型中血流和血栓成分的模型中静脉血栓形成的大小有贡献。这项研究还证明了使用多种小鼠模型来评估给定蛋白质在静脉血栓形成中的作用的重要性。
The intrinsic pathway factors (F) XII and FXI have been shown to contribute to thrombosis in animal models. We assessed the role of FXII and FXI in venous thrombosis in three distinct mouse models. Venous thrombosis was assessed in mice genetically deficient for either FXII or FXI. Three models were used: the inferior vena cava (IVC) stasis, IVC stenosis, and femoral vein electrolytic injury models. In the IVC stasis model, FXII and FXI deficiency did not affect the size of thrombi but their absence was associated with decreased levels of fibrin(ogen) and an increased level of the neutrophil extracellular trap marker citrullinated histone H3. In contrast, a deficiency of either FXII or FXI resulted in a significant and equivalent reduction in thrombus weight and incidence of thrombus formation in the IVC stenosis model. Thrombi formed in the IVC stenosis model contained significantly higher levels of citrullinated histone H3 compared with the thrombi formed in the IVC stasis model. Deletion of either FXII or FXI also resulted in a significant and equivalent reduction in both fibrin and platelet accumulation in the femoral vein electrolytic injury model. Collectively, these data indicate that FXII and FXI contribute to the size of venous thrombosis in models with blood flow and thrombus composition in a stasis model. This study also demonstrates the importance of using multiple mouse models to assess the role of a given protein in venous thrombosis.
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DOI：
10.1111/jth.12510
发表时间：
2014-04
期刊：
Journal of thrombosis and haemostasis : JTH
影响因子：
--
作者：
Geddings J;Aleman MM;Wolberg A;von Brühl ML;Massberg S;Mackman N
通讯作者：
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DOI：
10.1056/nejmoa1405760
发表时间：
2015-01-15
期刊：
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影响因子：
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作者：
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DOI：
10.1161/atvbaha.116.306925
发表时间：
2016-07
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
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作者：
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通讯作者：
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影响因子：
15.9
作者：
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通讯作者：
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DOI：
10.1161/atvbaha.111.225334
发表时间：
2011-06-01
影响因子：
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作者：
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Cooley, Brian C.