ADAMTS13 exerts a thrombolytic effect in microcirculation
ADAMTS13 exerts a thrombolytic effect in microcirculation
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DOI：
10.1160/th12-01-0046
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发表时间：
2012-09-01
影响因子：
6.7
通讯作者：
Wagner, Denisa D.
中科院分区：
文献类型：
--
作者：
Crescente, Marilena;Thomas, Grace M.;Wagner, Denisa D.
重组组织型纤溶酶原激活剂(r-tPA)是溶栓治疗的首选药物，但它有很大的出血风险，而且并不总是有效的。通过裂解血管性假血友病因子(von Willebrand factor，VWF)，金属蛋白酶ADAMTS13(一种去整合素样金属蛋白酶，与凝血酶反应蛋白I重复序列-13)下调受损血管的血栓形成。我们研究了重组ADAMTS13(r-ADAMTS13)是否能在小鼠体内诱导血栓溶解。血栓形成是由三氯化铁(FeCl3)诱导的背侧皮皱室小静脉损伤造成的。将磷酸盐缓冲盐水(PBS，Vehicle)、r-tPA或r-ADAMTS13加水飞蓟素(以阻止正在进行的凝血酶生成)直接应用于闭塞血管，并通过活体显微镜评估血栓溶解情况。与PBS相比，r-ADAMTS13治疗后30分钟(分钟)血流恢复的发生率显著增加(60%比0%，P
Recombinant tissue plasminogen activator (r-tPA) is the drug of choice for thrombolysis, but it is associated with a significant risk of bleeding and is not always successful. By cleaving von Willebrand factor (VWF), the metalloprotease ADAMTS13 (a disintegrin-like and metalloprotease with thrombospondin type I repeats-13) down-regulates thrombus formation in injured vessels. We investigated whether recombinant ADAMTS13 (r-ADAMTS13) induces thrombolysis in vivo in mice. Thrombosis was produced by ferric chloride-induced (FeCl3) injury in the venules of a dorsal skinfold chamber. Phosphate-buffered saline (PBS, vehicle), r-tPA or r-ADAMTS13, supplemented with hirudin (to stop ongoing thrombin generation), was directly applied onto the occluded vessel, and thrombus dissolution was evaluated by intravital microscopy. The incidence of blood flow restoration significantly increased 30 minutes (min) after r-ADAMTS13 vs. PBS treatment (60% vs. 0%, p