Vascular smooth muscle-derived tissue factor is critical for arterial thrombosis after ferric chloride-induced injury
Vascular smooth muscle-derived tissue factor is critical for arterial thrombosis after ferric chloride-induced injury
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DOI：
10.1182/blood-2007-05-090944
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发表时间：
2009-01-15
期刊：
影响因子：
20.3
通讯作者：
Taubman, Mark B.
中科院分区：
文献类型：
--
作者：
Wang, Li;Miller, Christine;Taubman, Mark B.
组织因子（Tissue factor， TF）启动凝血、调节止血，在介导动脉血栓形成中起关键作用。在动脉粥样硬化和动脉损伤中，TF在血管平滑肌细胞（VSMCs）中表达上调。为了研究vsmc衍生的TF的生物学作用，我们将TFflox/ flox小鼠与SM22 α Cre（+/-）小鼠杂交。TF缺乏小鼠主动脉介质中TF mRNA和活性分别降低96%和94.8%。血浆和浓缩微粒中测定的TF活性无差异。tf缺陷小鼠以预期的频率产生，没有出血或死亡率增加的证据，并且具有相似的激活部分凝血活酶和尾静脉出血时间。在vsmc特异性tf缺陷患者中，颈动脉氯化铁损伤后血栓介导的血流减少明显减弱。12只野生型小鼠中有11只出现稳定闭塞，而16只vsmc特异性tf缺陷小鼠中只有6只出现稳定闭塞（P=.001）。这些数据表明，vsmc衍生的TF在动脉血栓形成的大血管模型中至关重要。该小鼠模型在确定vsmc来源的TF在其他TF介导的现象（如再狭窄）中的作用方面应该是有价值的。（Blood. 2009; 113: 705-713）
Tissue factor (TF) initiates coagulation, regulates hemostasis, and plays a critical role in mediating arterial thrombosis. TF is up-regulated in vascular smooth muscle cells (VSMCs) in atherosclerosis and arterial injury. To examine the biologic role of VSMC-derived TF, we crossed TFflox/ flox mice with SM22 alpha Cre(+/-) mice. TF mRNA and activity were decreased in the aortic media of TF-deficient mice by 96% and 94.8%, respectively. There were no differences in TF activity measured in plasma or concentrated microparticles. TF-deficient mice were generated with the expected frequency, showed no evidence of bleeding or increased mortality, and had similar activated partial thromboplastin and tail vein bleeding times. Thrombus-mediated flow reduction in response to ferric chloride injury of the carotid arteries was significantly attenuated in VSMC-specific TF-deficient. Stable occlusion was seen in 11 of 12 wild-type mice, but in only 6 of 16 VSMC-specific TF-deficient mice (P=.001). These data suggest that VSMC-derived TF is critical in a macrovascular model of arterial thrombosis. This mouse model should be valuable in determining the contribution of VSMC-derived TF in other TF-mediated phenomena, such as restenosis. (Blood. 2009; 113: 705-713)