Ecotin: Exploring a feasible antithrombotic profile.
Ecotin: Exploring a feasible antithrombotic profile.
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Ecotin：探索可行的抗血栓方案。
DOI：
10.1016/j.ijbiomac.2015.03.071
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发表时间：
2015
影响因子：
8.2
通讯作者：
Zingali,RussolinaBenedeta
中科院分区：
文献类型：
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作者：
Wermelinger,LucianaSerrão;Frattani,FláviaSerra;Carneiro-Lobo,TatianaCorrea;Craik,CharlesS;Castro,HelenaCarla;Zingali,RussolinaBenedeta
Ecotin是大肠杆菌衍生的蛋白，可以抑制丝氨酸蛋白酶。有人建议，这种蛋白（ecotin-WT）及其一些变体可用于开发治疗血栓形成的原型。在这项工作中，我们分析了ecotin-WT及其携带两个突变（Met84Arg和Met85Arg， ecotin-RR）的变体的作用，以确定它们在体内模型中预防血栓形成的能力。玻璃体凝血试验中分析ecotin。采用动物模型和肺血栓形成小鼠模型观察其抗血栓活性。在使用尾巴横断模型的大鼠中，出血时间被评估为可能由这些蛋白质引起的副作用。Ecotin-RR对凝血酶的抑制作用优于ecotin-WT。两种ecotin表现出相似的抗凝活性机制，并能减少血栓的形成。相比之下，只有ecotin-RR在体外血栓栓塞模型中提高了生存率，增强了ecotin-RR的抗血栓活性。Ecotin-WT和ecotin-RR表现出有效的抗血栓作用，与出血无关。结果表明，ecotin-WT和ecotin-RR可能是开发抗凝分子的新支架。
Ecotin is anEscherichia coli-derived protein that can inhibit serine proteases. It has been suggested that this protein (ecotin-WT) and some of its variants could be used to develop a prototype to treat thrombosis. In this work, the effect of ecotin-WT and a variant of this protein harboring two mutations (Met84Arg and Met85Arg, ecotin-RR) were analyzed to determine their ability to prevent thrombus formation usingin vivomodels. Ecotins were analyzedin vitrousing the coagulation tests. Anin vivovenous thrombosis rat model and a pulmonary thromboembolism mouse model were used to investigate the antithrombotic activity. The bleeding time in rats using a tail-transection model was evaluated as a possible side effect caused by the administration of these proteins. Ecotin-RR was more effective in inhibiting thrombin than ecotin-WT. Both ecotins presented similar mechanisms of anticoagulation activity and were able to decrease thrombus formation. In contrast, only ecotin-RR increased survival rates in thein vivopulmonary thromboembolism model, reinforcing the antithrombotic activity of ecotin-RR. Ecotin-WT and more so ecotin-RR showed potent antithrombotic effects, not associated with bleeding. The presented results indicate that ecotin-WT and ecotin-RR may be new scaffolds that could be used to develop anticoagulation molecules.