The frequent Marburg I polymorphism impairs the pro-urokinase activating potency of the factor VII activating protease (FSAP)
The frequent Marburg I polymorphism impairs the pro-urokinase activating potency of the factor VII activating protease (FSAP)
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DOI：
10.1097/00001721-200207000-00008
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发表时间：
2002-07-01
影响因子：
1.1
通讯作者：
Weimer, T
中科院分区：
文献类型：
--
作者：
Roemisch, J;Feussner, A;Weimer, T
最近报道的血浆因子七激活蛋白酶（FSAP）也被发现是尿激酶原[尿型单链纤溶酶原激活剂（scuPA）]的有效激活剂。最初的流行病学研究令人惊讶地表明，5-10%的健康献血者的血浆具有激活scuPA的受损潜力。对各基因组DNA的分析揭示了FSAP的一种特定的单核苷酸多态性，其导致相同的氨基酸交换（G511 E），这与活性降低相关。相应的突变被命名为FSAP马尔堡L。进行野生型和突变型血浆的血栓弹力图，通过添加硫酸葡聚糖（DXS）促进内在FSAP酶原的自激活，并通过添加scuPA加速凝块溶解。在这些条件下，组织因子诱导的凝血显示，与野生型血浆相比，马尔堡I突变血浆中的凝块溶解显著延迟。此外，在DXS和scuPA的存在下，FSAP缺陷型血浆显示出显著延长的血浆凝块溶解时间，而添加纯化的FSAP酶原加scuPA逆转了这种效果。这些结果支持FSAP有助于scuPA依赖性血浆纤维蛋白溶解潜力的假设，例如，在含有FSAP马尔堡I多态性的血浆中，scuPA依赖性血浆纤维蛋白溶解潜力可能受损。(C)2002年利平科特威廉姆斯威尔金斯。
The recently reported plasmatic, Factor Seven Activating Protease (FSAP), has also been found to be a potent activator of prourokinase [single-chain plasminogen activator, urinary type (scuPA)]. An initial epidemiological study surprisingly showed that plasmas of 5-10% of healthy blood donors had an impaired potential to activate scuPA. Analysis of the respective genomic DNAs revealed one particular single nucleotide polymorphism of FSAP resulting in an identical amino acid exchange (G511E), which correlates with the reduced activities. The corresponding mutation was named FSAP Marburg L Thrombelastographies of wild-type and mutant plasmas were performed, facilitating the auto-activation of the intrinsic FSAP pro-enzymes by addition of dextran sulfate (DXS) and accelerated clot lysis by addition of scuPA. On these conditions, tissue-factor-induced coagulation revealed that clot lysis was significantly delayed in the Marburg I mutant plasmas as compared with wild-type plasmas. Furthermore, in the presence of DXS and scuPA, a FSAP-deficient plasma revealed significantly prolonged plasma clot lysis times, whereas the addition of purified FSAP pro-enzyme plus scuPA reversed this effect. These results support the hypothesis that FSAP contributes to the scuPA-dependent plasma fibrinolytic potential, which can be impaired in plasmas containing the FSAP Marburg I polymorphism, for instance. (C) 2002 Lippincott Williams Wilkins.