It has been shown that lipoprotein(a) (Lp[a]) may interfere with the fibrinolytic system and that the Lp(a) level in an individual remains constant. To evaluate the effects of Lp(a) on the fibrinolytic system in patients with unstable angina, we measured plasma levels of Lp(a), the alpha 2-plasmin inhibitor-plasmin complex, and the thrombin-antithrombin III complex. The latter is a marker of th...

A nephritogenic antigen for acute poststreptococcal glomerulonephritis (APSGN) was isolated recently from group A streptococcus and termed nephritis-associated plasmin receptor (NAPlr). In vitro experimental data indicate that the pathogenic role of NAPlr occurs through its ability to bind to plasmin and maintain its proteolytic activity. However, the mechanism whereby this antigen induces glom...

Plasmin not only functions as a key enzyme in the fibrinolytic system but also directly inactivates factor VIII and other clotting factors such as factor V. However, the mechanisms of plasmin-catalyzed factor VIII inactivation are poorly understood. In this study, levels of factor VIII activity increased approximately 2-fold within 3 min in the presence of plasmin, and subsequently decreased to...

Kunitz domain 1 (KD1) of tissue factor pathway inhibitor-2 in which P2' residue Leu17 (bovine pancreatic trypsin inhibitor numbering) is mutated to Arg selectively inhibits the active site of plasmin with ∼5-fold improved affinity. Thrombin cleavage (24 h extended incubation at a 1:50 enzyme-to-substrate ratio) of the KD1 mutant (Leu17Arg) yielded a smaller molecule containing the intact Kunitz...

Alzheimer disease is characterized by the presence of increased levels of the β-amyloid peptide (Aβ) in the brain parenchyma and cerebral blood vessels. This accumulated Aβ can bind to fibrin(ogen) and render fibrin clots more resistant to degradation. Here, we demonstrate that Aβ(42) specifically binds to fibrin and induces a tighter fibrin network characterized by thinner fibers and increased...

We previously showed that the kringle domains of plasmin and angiostatin, the N-terminal four kringles (K1-4) of plasminogen, directly bind to integrins. Angiostatin blocks tumor-mediated angiogenesis and has great therapeutic potential. Angiostatin binding to integrins may be related to the antiinflammatory action of angiostatin. We reported that plasmin induces signals through protease-activa...

BACKGROUND Plasmin is a serine protease that plays a critical role in fibrinolysis, which is a process that prevents blood clots from growing and becoming problematic. Recombinant human microplasminogen (rhμPlg) is a derivative of plasmin that solely consists of the catalytic domain of human plasmin and lacks the five kringle domains found in the native protein. Developing an industrial product...

Alzheimer disease is characterized by the presence of increased levels of the amyloid peptide (A ) in the brain parenchyma and cerebral blood vessels. This accumulated A can bind to fibrin(ogen) and render fibrin clots more resistant to degradation. Here, we demonstrate that A 42 specifically binds to fibrin and induces a tighter fibrin network characterized by thinner fibers and increased resi...

Recruitment of the serine protease plasmin is central to the pathogenesis of many bacterial species, including Group A streptococcus (GAS), a leading cause of morbidity and mortality globally. A key process in invasive GAS disease is the ability to accumulate plasmin at the cell surface, however the role of host activators of plasminogen in this process is poorly understood. Here, we demonstrat...

The urokinase receptor (uPAR) coordinates plasmin-mediated cell-surface proteolysis and promotes cellular adhesion via a binding site for vitronectin on uPAR. Because vitronectin also binds plasminogen activator inhibitor type 1 (PAI-1), and plasmin cleavage of vitronectin reduces PAI-1 binding, we explored the effects of plasmin and PAI-1 on the interaction between uPAR and vitronectin. PAI-1 ...