Macrovascular thrombosis is driven by tissue factor derived primarily from the blood vessel wall
Macrovascular thrombosis is driven by tissue factor derived primarily from the blood vessel wall
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DOI：
10.1182/blood-2004-06-2225
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发表时间：
2005-01-01
期刊：
影响因子：
20.3
通讯作者：
Fay, WP
中科院分区：
文献类型：
--
作者：
Day, SM;Reeve, JL;Fay, WP
白细胞和白细胞衍生的微粒含有低水平的组织因子（TF）并合并形成血栓。虽然这个循环池的TF在血栓形成中起着关键作用，但相对于血管壁TF的功能意义尚不明确。我们验证了白细胞衍生的TF有助于体内血栓形成的假设。与野生型小鼠相比，严重TF缺乏（即TF-/-、hTF-Tg（+）或“低TF”）的小鼠在颈动脉损伤或下腔静脉结扎后血栓形成明显受损。骨髓移植策略被用来调节白细胞来源的TF水平。将低tf骨髓移植到野生型小鼠体内，不抑制动脉或静脉血栓的形成。同样，将野生型骨髓移植到低tf小鼠体内也不会加速血栓形成。体外分析显示，血液中的TF活性非常低，并且明显超过血管壁中的活性。因此，我们的研究结果表明，动脉和静脉大血管中的血栓形成主要是由来自血管壁的TF驱动的，而不是由白细胞驱动的。
Leukocytes and leukocyte-derived microparticles contain low levels of tissue factor (TF) and incorporate into forming thrombi. Although this circulating pool of TF has been proposed to play a key role in thrombosis, its functional significance relative to that of vascular wall TF is poorly defined. We tested the hypothesis that leukocyte-derived TF contributes to thrombus formation in vivo. Compared to wild-type mice, mice with severe TF deficiency (ie, TF-/-, hTF-Tg(+), or "low-TF") demonstrated markedly impaired thrombus formation after carotid artery injury or inferior vena cava ligation. A bone marrow transplantation strategy was used to modulate levels of leukocyte-derived TF. Transplantation of low-TF marrow into wild-type mice did not suppress arterial or venous thrombus formation. Similarly, transplantation of wild-type marrow into low-TF mice did not accelerate thrombosis. In vitro analyses revealed that TF activity in the blood was very low and was markedly exceeded by that present in the vessel wall. Therefore, our results suggest that thrombus formation in the arterial and venous macrovasculature is driven primarily by TF derived from the blood vessel wall as opposed to leukocytes.