Heparanase增强激活因子X一代的组织因子和激活因子七世的存在。
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Brenner最低点Y, B, Fux L, Shafat I, J•阿蒂亚斯,Vlodavsky我
Heparanase增强激活因子X一代的组织因子和激活因子七世的存在。
Haematologica。2010年11月,95 (11):1927 - 34。doi: 10.3324 / haematol.2010.023713。Epub 2010年7月15日。
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20634491 (在PubMed]
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背景:Heparanase是endo-beta-D-glucuronidase主导性参与肿瘤转移和血管生成。最近,我们证明了heparanase参与止血的监管系统。我们的假设是,heparanase直接参与激活凝血级联的。设计和方法:激活因子X和使用显色测定凝血酶进行了研究,免疫印迹和thromboelastography。Heparanase水平通过酶联免疫吸附试验测定。潜在的组织因子之间的直接交互,heparanase研究co-immunoprecipitation和偏远的化验。结果:有趣的是,除了heparanase组织因子和激活因子VII导致增加3到4倍的激活凝血级联如图所示增加激活因子X和凝血酶的生产。培养基的人类胚胎肾293个细胞过度表达heparanase及其衍生物non-enzymatic方式激活因子X水平增加。heparanase添加到混合的正常血浆时,增加一个7 - 8倍激活因子X观察水平。随后,我们寻找heparanase必威国际app的临床数据支持这种新发现的作用。 Plasma samples from 35 patients with acute leukemia at presentation and 20 healthy donors were studied for heparanase and activated factor X levels. A strong positive correlation was found between plasma heparanase and activated factor X levels (r=0.735, P=0.001). Unfractionated heparin and an inhibitor of activated factor X abolished the effect of heparanase, while tissue factor pathway inhibitor and tissue factor pathway inhibitor-2 only attenuated the procoagulant effect. Using co-immunoprecipitation and far-western analyses it was shown that heparanase interacts directly with tissue factor. CONCLUSIONS: Overall, our results support the notion that heparanase is a potential modulator of blood hemostasis, and suggest a novel mechanism by which heparanase increases the generation of activated factor X in the presence of tissue factor and activated factor VII.