Myeloid cell tissue factor does not contribute to venous thrombogenesis in an electrolytic injury model.

Myeloid cell tissue factor does not contribute to venous thrombogenesis in an electrolytic injury model.
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DOI:
10.1016/j.thromres.2011.11.027
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发表时间:
2012-10
影响因子:
7.5
通讯作者:
Myers DD Jr
Myers DD Jr
中科院分区:
医学3区
文献类型:
--
作者:
Hampton AL;Diaz JA;Hawley AE;Wrobleski SK;Wang JG;Lee RD;Kirchhofer D;Sigler RE;Wakefield TW;Mackman N;Myers DD Jr

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组织因子(TF)是外源性凝血级联的有效发起者。TF在静脉血栓性疾病中的作用和来源尚不清楚。我们的研究目的是确定骨髓细胞TF对小鼠静脉血栓形成的贡献。采用小鼠下腔静脉电解模型诱导血栓形成。各组小鼠采用(1)TFflox/floxLysMCre+小鼠降低骨髓细胞中TF表达,(2)TFflox/floxLysMCre-同窝小鼠对照,(3)野生型小鼠给予单克隆抗小鼠TF抗体(1H1)抑制TF活性,(4)野生型小鼠给予大鼠IgG。基线、血栓形成后第2天和第6天的评估包括血栓重量、静脉壁炎症细胞迁移、静脉壁TF mRNA和血浆d -二聚体水平。抑制TF可显著降低静脉血栓形成后2天的血栓重量。相比之下,与对照组相比,TFflox/floxLysMCre+的血栓重量没有变化。骨髓细胞TF的缺失不影响中性粒细胞或单核细胞向静脉壁的浸润。静脉壁TF mRNA表达在第2天下降,但在血栓形成后第6天恢复到基线水平。d -二聚体水平在有或没有骨髓细胞TF的小鼠血栓形成后2天达到峰值。TF在大血管静脉血栓的形成中起重要作用。然而,在该模型中,骨髓细胞表达TF并没有显著促进静脉血栓形成。
Tissue factor (TF) is a potent initiator of the extrinsic coagulation cascade. The role and source of TF in venous thrombotic disease is not clearly defined. Our study objective was to identify the contribution of myeloid cell TF to venous thrombogenesis in mice. The mouse electrolytic inferior vena cava model was used to induce thrombosis. The following groups of mice were used (1) TFflox/floxLysMCre+ mice that have reduced TF expression in myeloid cells, (2) TFflox/floxLysMCre- littermate controls, (3) Wild type mice given a monoclonal anti-mouse TF antibody (1H1) to inhibit TF activity, and (4) Wild type mice given rat IgG. Evaluations at baseline, day 2, and day 6 post thrombosis included thrombus weight, vein wall inflammatory cell migration, vein wall TF mRNA, and plasma D-dimer levels. Inhibition of TF significantly decreased thrombus weight 2 days post venous thrombosis. In contrast, TFflox/floxLysMCre+ had no change in thrombus weight when compared to littermate controls. The absence of myeloid cell TF did not affect infiltration of neutrophils or monocytes into the vein wall. TF mRNA expression in the vein wall decreased at 2 days but then returned to baseline levels by 6 days post thrombosis. D-dimer levels peaked at 2 days post thrombosis in mice with or without myeloid cell TF. TF is important in the formation of venous thrombi in the macrovasculature. However, TF expression by myeloid cells does not significantly contribute to venous thrombogenesis in this model.
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