更新于：2024-11-01

Fibrinogen x Plasminogen activators

更新于：2024-11-01

基本信息

关联

项与 Fibrinogen x Plasminogen activators 相关的药物

Plasmin

纤溶酶

靶点

Fibrinogen x Plasminogen activators

作用机制

纤维蛋白原抑制剂 [+1]

在研机构

吉林津升制药有限公司 [+1]

原研机构

北京赛升药业股份有限公司

在研适应症

脑梗塞 [+2]

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

中国

首次获批日期1999-01-01

100 项与 Fibrinogen x Plasminogen activators 相关的临床结果

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100 项与 Fibrinogen x Plasminogen activators 相关的转化医学

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0 项与 Fibrinogen x Plasminogen activators 相关的专利（医药）

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108

项与 Fibrinogen x Plasminogen activators 相关的文献（医药）

2018-10-01·Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease2区 · 生物学

Altered structure and function of fibrinogen after cleavage by Factor VII Activating Protease (FSAP)

2区 · 生物学

Article

作者: Lochnit, Günther ; Undas, Anetta ; Hanschmann, Kai-Martin ; Lang, Irene M ; Kanse, Sandip M ; Etscheid, Michael ; Zabczyk, Michal ; Subramaniam, Saravanan

Factor VII Activating Protease (FSAP) is a plasma protease affecting both coagulation and fibrinolysis. Although a role in hemostasis is still unclear, the identification of additional physiologic substrates will help to elucidate its role in this context. FSAP has been reported to cleave fibrinogen, but the functional consequences of this are not known. We have therefore undertaken this study to determine the implications of this cleavage for fibrin-clot formation and its lysis. Treatment of human fibrinogen with FSAP released an N-terminal peptide from the Bβ chain (Bβ1-53) and subsequently the fibrinopeptide B; within the Aα chain a partial truncation of the αC-region by multiple cleavages was seen. The truncated fibrinogen showed a delayed thrombin-catalyzed polymerization and formed fibrin clots of reduced turbidity, indicative of thinner fibrin fibers. Confocal laser scanning and scanning electron microscopy of these clots revealed a less coarse fibrin network with thinner fibers and a smaller pore size. A lower pore size was also seen in permeability studies. Unexpectedly, FSAP-treated fibrinogen or plasma exhibited a significantly faster tPA-driven lysis, which correlated exclusively with cleavage of fibrinogen and not with activation of plasminogen activators. Similar observations were also made in plasma after activation of endogenous zymogen FSAP, but not in plasma of carrier of the rare Marburg I single nucleotide polymorphism. In conclusion, altering fibrin clot properties by fibrinogenolysis is a novel function of FSAP in the vasculature, which facilitates clot lysis and may in vivo contribute to reduced fibrin deposition during thrombosis.

2017-01-01·Thrombosis and Haemostasis2区 · 医学

Fibrin clot structure - pro-fibrinolytic effect of oral contraceptives in apparently healthy women

2区 · 医学

Article

作者: Johannes Jakobsen Sidelmann ; Andrea H. Krug ; Ulrich Winkler ; Jørgen Jespersen ; Jørgen Brodersen Gram ; Cornelis Kluft

SummaryFibrin metabolism is influenced by many factors. The velocity of fibrin formation, genetic polymorphisms, fibrinolytic features and the structure of the fibrin clot are determinants of fibrin turnover. Oral contraceptives (OCs) have significant impact on the haemostatic system, by increasing the concentration of coagulation factors, plasminogen and tissue plasminogen activator activity, and decreasing the concentration of haemostatic inhibitors. The present study addresses the influence of OCs on fibrin structure and fibrin metabolism. The study included 70 women treated with seven different OC-formulations. Blood was collected at baseline and after six months of OCs. The plasma concentration of fibrinogen, thrombin-antithrombin complex (TAT), plasminogen, plasmin-antiplasmin complex (PAP), D-Dimer and thrombin generation measures were determined. Fibrin structure measures and fibrin clot lysis not affected by the plasma concentration of plasminogen activators and inhibitors were determined. OCs increased the concentration of fibrinogen, TAT, plasminogen, PAP and D-dimer significantly and affected measures of thrombin generation (p<0.001). The maximal optical density of fibrin (p<0.001), the fibrin fibre density (p=0.03), fibrin fibre diameter (p=0.003), fibrin mass-length ratio (p<0.001) and lysis per hour (p<0.001) increased significantly upon OC-treatment. Lysis per hour was not correlated to the concentration of plasminogen. We conclude that the effect of OCs on the coagulation system is balanced by alterations in fibrin structure, facilitating clot lysis and contributing to the fibrinolytic susceptibility already present in women treated with OC. These alterations may counterbalance the OC-induced increased thrombin generation and reduced coagulation inhibitory potential, contributing to maintenance of the haemostatic balance in women receiving OCs.

2016-12-01·European Journal of Clinical Microbiology & Infectious Diseases3区 · 医学

The remarkably multifunctional fibronectin binding proteins of Staphylococcus aureus

3区 · 医学

Review

作者: Foster, T J

Staphylococcus aureus expresses two distinct but closely related multifunctional cell wall-anchored (CWA) proteins that bind to the host glycoprotein fibronectin. The fibronectin binding proteins FnBPA and FnBPB comprise two distinct domains. The C-terminal domain comprises a tandem array of repeats that bind to the N-terminal type I modules of fibronectin by the tandem β-zipper mechanism. This causes allosteric activation of a cryptic integrin binding domain, allowing fibronectin to act as a bridge between bacterial cells and the α₅β₁ integrin on host cells, triggering bacterial uptake by endocytosis. Variants of FnBPA with polymorphisms in fibronectin binding repeats (FnBRs) that increase affinity for the ligand are associated with strains that infect cardiac devices and cause endocarditis, suggesting that binding affinity is particularly important in intravascular infections. The N-terminal A domains of FnBPA and FnBPB have diverged into seven antigenically distinct isoforms. Each binds fibrinogen by the 'dock, lock and latch' mechanism characteristic of clumping factor A. However, FnBPs can also bind to elastin, which is probably important in adhesion to connective tissue in vivo. In addition, they can capture plasminogen from plasma, which can be activated to plasmin by host and bacterial plasminogen activators. The bacterial cells become armed with a host protease which destroys opsonins, contributing to immune evasion and promotes spreading during skin infection. Finally, some methicillin-resistant S. aureus (MRSA) strains form biofilm that depends on the elaboration of FnBPs rather than polysaccharide. The A domains of the FnBPs can interact homophilically, allowing cells to bind together as the biofilm accumulates.