Platelets, glycoprotein Ib-IX, and von Willebrand factor are required for FeCl(3)-induced occlusive thrombus formation in the inferior vena cava of mice.
Platelets, glycoprotein Ib-IX, and von Willebrand factor are required for FeCl(3)-induced occlusive thrombus formation in the inferior vena cava of mice.
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DOI：
10.3109/09537104.2012.696746
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发表时间：
2013
期刊：
影响因子：
3.3
通讯作者：
Gartner TK
中科院分区：
文献类型：
--
作者：
Joglekar MV;Ware J;Xu J;Fitzgerald ME;Gartner TK
静脉血栓栓塞是心血管疾病死亡的主要原因。尽管糖蛋白 (GP) Ib-IX/血管性血友病因子 (vWF) 轴在动脉血栓形成中很重要，但其在响应内皮损伤（而非狭窄或瘀滞）的静脉血栓而非小静脉血栓形成中的需求尚不明确。在下腔静脉 (IVC) 中评估了 GPIbα-vWF 参与 FeCl3 诱导的血栓形成的情况。研究了 FeCl3 诱导的下腔静脉损伤后稳定、闭塞的血栓形成。 FeCl3（20% FeCl3，10 分钟）诱导的闭塞性血栓形成需要血小板，这通过血小板减少小鼠中缺乏闭塞以及对照动物中的稳定闭塞证实。使用 GPIbα 缺陷动物（人类 Bernard-Soulier 综合征 (BSS) 模型）未观察到 IVC 闭塞。研究了转基因 IL-4R/GPIbα 小鼠（缺乏鼠 GPIbα，但表达与人 GPIbα 的跨膜和细胞质结构域融合的人白细胞介素 (IL)-4 受体的细胞外结构域），以确定 BSS 小鼠中 IVC 闭塞的缺失是否是由 GPIbα 细胞外结构域缺陷而不是血小板 BSS 引起的 表型相关异常。与 GPIbα 敲除 (KO) 小鼠一样，IL-4R/GPIbα 小鼠的 IVC 中未观察到闭塞。 vWF 缺陷小鼠的 IVC 也未能响应 FeCl3 治疗而闭塞。嵌合蛋白 GPIbα(2V)-Fc 可防止闭塞，表明 GPIbα-vWF A1 结构域相互作用是 FeCl3 诱导 IVC 中稳定血栓形成所必需的。因此，尽管 IVC 直径大且静脉流速低，但 FeCl3 诱导的 IVC 中稳定、闭塞性血栓形成是血小板、GPIbα-vWF 相互作用依赖性的。
Venous thromboembolism is a leading cause of death from cardiovascular disease. Despite the importance of the glycoprotein (GP) Ib-IX/von Willebrand factor (vWF) axis in arterial thrombosis, its requirement in venous, not venule thrombosis in response to endothelial injury (not stenosis or stasis) is uncharacterized. GPIbα-vWF participation in FeCl3-induced thrombus formation was evaluated in the inferior vena cava (IVC). Stable, occlusive thrombus formation in response to FeCl3-induced injury of the IVC was studied. FeCl3 (20% FeCl3, 10 minutes)-induced occlusive thrombosis required platelets as confirmed by a lack of occlusion in thrombocytopenic mice, and stable occlusion in control animals. No IVC occlusion was observed using GPIbα-deficient animals, a model of the human Bernard-Soulier syndrome (BSS). Transgenic IL-4R/GPIbα mice (lack murine GPIbα, but express the extracellular domain of the human interleukin (IL)-4 receptor fused to the transmembrane and cytoplasmic domains of human GPIbα), were studied to determine if the absence of IVC occlusion in the BSS mouse was caused by GPIbα extracellular domain deficiency rather than platelet BSS phenotype associated abnormalities. As with GPIbα knock-out (KO) mice, no occlusion was observed in the IVC of IL-4R/GPIbα mice. The IVC of vWF-deficient mice also failed to occlude in response to FeCl3 treatment. The chimeric protein GPIbα(2V)-Fc prevented occlusion, demonstrating that GPIbα-vWF A1 domain interaction is required for FeCl3-induced stable thrombus formation in the IVC. Therefore, FeCl3-induced stable, occlusive thrombus formation in the IVC is platelet, GPIbα-vWF interaction-dependent despite the large diameter and low venous flow rate in the IVC.
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影响因子：
7.3
作者：
Elvers M;Stegner D;Hagedorn I;Kleinschnitz C;Braun A;Kuijpers ME;Boesl M;Chen Q;Heemskerk JW;Stoll G;Frohman MA;Nieswandt B
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10.1073/pnas.0608422104
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