Fibrinogen and Antifibrinolytic Proteins: Interactions and Future Therapeutics.

Fibrinogen and Antifibrinolytic Proteins: Interactions and Future Therapeutics.
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纤维蛋白原和抗纤溶蛋白:相互作用和未来的治疗。

DOI:
10.3390/ijms222212537
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发表时间:
2021-11-21
影响因子:
5.6
通讯作者:
Ajjan RA
Ajjan RA
中科院分区:
生物学2区
文献类型:
--
作者:
Pechlivani N;Kearney KJ;Ajjan RA

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血栓形成仍然是世界范围内发病率和死亡率的主要原因。目前的抗血小板和抗凝治疗在减少血管事件方面是有效的,但以增加出血风险为代价。靶向与纤维蛋白原相互作用且参与纤溶功能减退的蛋白质代表了开发有效且安全的治疗剂的更具体方法。抗纤溶蛋白α-2抗纤溶酶(α2AP)、凝血酶激活的纤溶抑制物(TAFI)、补体C3和纤溶酶原激活物抑制物-2(派-2)可通过FXIIIa掺入纤维蛋白凝块中并通过不同机制影响纤溶。因此,这些抗纤维蛋白溶解蛋白是开发新疗法的有吸引力的靶标,既用于调节血栓形成风险,也用于潜在地改善出血性疾病中的凝块不稳定性。本文综述了纤维蛋白原结合的抗纤溶蛋白的主要特性,它们对血块溶解的影响以及与血栓或出血性疾病的关系。这些蛋白质的作用,靶向血栓性疾病或出血性疾病的纤溶系统的治疗策略也进行了讨论。
Thrombus formation remains a major cause of morbidity and mortality worldwide. Current antiplatelet and anticoagulant therapies have been effective at reducing vascular events, but at the expense of increased bleeding risk. Targeting proteins that interact with fibrinogen and which are involved in hypofibrinolysis represents a more specific approach for the development of effective and safe therapeutic agents. The antifibrinolytic proteins alpha-2 antiplasmin (α2AP), thrombin activatable fibrinolysis inhibitor (TAFI), complement C3 and plasminogen activator inhibitor-2 (PAI-2), can be incorporated into the fibrin clot by FXIIIa and affect fibrinolysis by different mechanisms. Therefore, these antifibrinolytic proteins are attractive targets for the development of novel therapeutics, both for the modulation of thrombosis risk, but also for potentially improving clot instability in bleeding disorders. This review summarises the main properties of fibrinogen-bound antifibrinolytic proteins, their effect on clot lysis and association with thrombotic or bleeding conditions. The role of these proteins in therapeutic strategies targeting the fibrinolytic system for thrombotic diseases or bleeding disorders is also discussed.
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