Reduced Plasminogen Binding and Delayed Activation Render γ′-Fibrin More Resistant to Lysis than γA-Fibrin

Abstract

Background: When compared with degradation of the predominant ␥ A -fibrin, lysis of variant ␥Ј-fibrin is delayed. Results: Thrombin-mediated fibrinopeptide B release is slower from ␥Ј-fibrinogen than from ␥ A -fibrinogen, resulting in delayed binding and activation of plasminogen. Conclusion: Delayed plasmin generation renders ␥Ј-fibrin resistant to lysis. Significance: The association between slower clotting and delayed lysis highlights the links between coagulation and fibrinolysis.

Sensing adhesion forces between erythrocytes and γ’ fibrinogen, modulating fibrin clot architecture and function

“…We also studied fibrin clots in the presence of 5% and 10% of RBCs by LSCM; however, the high number of Finally, we studied fibrinolysis of clots made with both fibrinogen variants ( Figure 7). In line with previous studies 21 , a significant increase in lysis time was observed for A ' compared with A A fibrin clots (15.82 ± 1.48 min vs. 10.54 ± 0.44 min, respectively; p = 0.0267).…”

“…Fibrin clots formed in the presence of the fibrinogen ' variant are more resistant to fibrinolysis, due to reduced binding of plasminogen and tissue plasminogen activator, leading to reduced plasmin generation 21 . Fibrinogen ' variant is associated with a heterogeneous, non-uniform clot structure, with more branch points than clots formed by A chains 6,22,23 .In addition, ' fibrinogen binds to thrombin exosite II 24 .…”

“…However these studies were conducted with a 10% hematocrit, where their diffusion may be increased. It was suggested that the slower lysis of ' clots is due to delayed fibrinopeptide B release, leading to a delay of plasminogen binding and activation 21 .…”

Fibrinogen splice variation and cross-linking: Effects on fibrin structure/function and role of fibrinogen γ′ as thrombomobulin II

“…The ' fibers pack significantly less protofibrils and are less stiff than A fibers [14]. While ' clots are mechanically impaired, they are more resistant to proteolysis by plasmin than A clots due to impaired conversion of plasminogen to plasmin by tissue plasminogen activator on ' clots [15]. The significance of these effects for health and disease is less clear since increased levels of fibrinogen ' have been associated with coronary artery disease and myocardial infarction on one hand, while decreased levels have been associated with venous thrombosis on the other [16].…”

Fibrin γ/γ' influences the secretion of fibrinolytic components and clot structure

“…However, this is the first time that the effects of fibrin(ogen) γ/ γ´ on endothelial cells are reported.The main finding of the present work is that fibrin(ogen) γ/ γ´ levels alter the secretion of the fibrinolytic components uPA and PAI 1 thus mimicking the effect of thrombin. In order to imitate physiological conditions or to reach pathological levels of fibrinogen γ/ γ´, this variant was mixed with fibrinogen γ/ γ, differing from previous studies where either purified[20][21][22]33] or recombinant[ 34,35] fibrinogen γ/ γ or fibrinogen γ/ γ´ were used.…”