Novel venous thromboembolism mouse model to evaluate the role of complete and partial factor XIII deficiency in pulmonary embolism risk.
Novel venous thromboembolism mouse model to evaluate the role of complete and partial factor XIII deficiency in pulmonary embolism risk.
复制标题
DOI：
10.1111/jth.15510
复制
发表时间：
2021-12
期刊：
影响因子：
--
通讯作者：
Wolberg AS
中科院分区：
文献类型：
--
作者：
Kattula S;Sang Y;de Ridder G;Silver AC;Bouck EG;Cooley BC;Wolberg AS
静脉血栓形成（VT）和肺栓塞（PE），统称静脉血栓栓塞（VTE），导致高死亡率和发病率。因子XIII（FXIII）交联纤维蛋白以增强血栓稳定性，因此可能影响PE风险。由于缺乏概括人类PE特征的模型，阐明导致PE的机制受到限制。开发一种允许富红细胞（RBC）和纤维蛋白VT栓塞的小鼠模型，并确定FXIII对PE风险的贡献。在凝血酶输注PE模型中，F13 a +/+、F13 a +/−和F13 a −/−小鼠的肺血栓发生率相似;然而，血栓较小，RBC含量较低（≤7%），与人PE不同（约70%）。为了确定产生与人类PE组织学特征一致的PE的模型，我们比较了小鼠股静脉电解损伤、股静脉FeCl 3损伤和VT的肾下腔静脉（IVC）停滞模型。电解和FeCl 3模型产生的血栓较小，红细胞较少（分别为5%和4%），而IVC淤滞产生的血栓较大，红细胞含量较高（68%），与人类PE相似。在IVC停滞和结扎线去除（解结扎）以允许血栓栓塞后，与F13 a +/+小鼠相比，F13 a +/−和F13 a −/−小鼠的PE发生率分别相似和增加。与基于凝血酶输注、电解损伤和FeCl 3的模型相比，IVC停滞产生的血栓在组织学上与人类血栓最为相似。IVC淤滞后再行结扎可栓塞现有的富含红细胞和纤维蛋白的血栓。FXIII完全缺乏可增加PE的发病率，但部分缺乏则不会。
Venous thrombosis (VT) and pulmonary embolism (PE), collectively venous thromboembolism (VTE), cause high mortality and morbidity. Factor XIII (FXIII) crosslinks fibrin to enhance thrombus stability and consequently may influence PE risk. Elucidating mechanisms contributing to PE is limited by a lack of models that recapitulate human PE characteristics. Develop a mouse model that permits embolization of red blood cell (RBC)- and fibrin-rich VT and determine the contribution of FXIII to PE risk. In a thrombin infusion PE model, F13a+/+, F13a+/−, and F13a−/− mice had similar incidence of lung thrombi; however, thrombi were small, with low RBC content (≤7%), unlike human PEs (~70%). To identify a model producing PE consistent with histological characteristics of human PE, we compared mouse femoral vein electrolytic injury, femoral vein FeCl3 injury, and infrarenal vena cava (IVC) stasis models of VT. Electrolytic and FeCl3 models produced small thrombi with few RBCs (5% and 4%, respectively), whereas IVC stasis produced large thrombi with higher RBC content (68%) that was similar to human PEs. After IVC stasis and ligature removal (de-ligation) to permit thrombus embolization, compared to F13a+/+ mice, F13a+/− and F13a−/− mice had similar and increased PE incidence, respectively. Compared to thrombin infusion-, electrolytic injury-, and FeCl3-based models, IVC stasis produces thrombi that are most histologically similar to human thrombi. IVC stasis followed by de-ligation permits embolization of existing RBC- and fibrin-rich thrombi. Complete FXIII deficiency increases PE incidence, but partial deficiency does not.
登录
查看更多内容
DOI：
10.1111/jth.14744
发表时间：
2020-04
期刊：
Journal of thrombosis and haemostasis : JTH
影响因子：
--
作者：
Kattula S;Bagoly Z;Tóth NK;Muszbek L;Wolberg AS
通讯作者：
Wolberg AS
影响因子：
9.6
作者：
Girard, P;Musset, D;Simonneau, G
通讯作者：
Simonneau, G
影响因子：
81.5
作者：
Huisman, Menno V.;Barco, Stefano;Klok, Frederikus A.
通讯作者：
Klok, Frederikus A.
DOI：
10.1161/atvbaha.111.225334
发表时间：
2011-06-01
影响因子：
8.7
作者：
Cooley, Brian C.
通讯作者：
Cooley, Brian C.
影响因子：
20.3
作者：
Byrnes, James R.;Duval, Cedric;Wolberg, Alisa S.
通讯作者：
Wolberg, Alisa S.