Copper ion binding and heparin interactions of human fibrinogen

Abstract

synopsisThe binding of copper ions to fibrinogen was studied by the equilibrium dialysis technique in neutral Tris buffer. The presence of copper causes precipitation of fibrinogencopper complexes, the amount of which varies with the copper ion concentration. Solutions of 96% clottable fibrinogen (whole fibrinogen) displayed a maximum binding capacity about four times greater than that of fibrinogen solutions from which the coldinsoluble precipitate had been removed (cold-soluble fibrinogen). Binding in both systems apparently involves two classes of sites in fibrinogen, and the class of lower affinity is associated with cooperative interactions with copper. The copper concentration a t which this cooperative uptake occurs is identical to the concentration at which the amount of precipitated material increases sharply and also to the concentration at which a sharp decrease is observed in the sedimentation coefficient of soluble fibrinogen, suggesting some relationship between copper binding, solubility, and solution properties.The presence of heparin markedly affects the sedimentation coefficient of fibrinogen in the presence of copper ions, although showing a lesser effect in the absence of the metal. The sedimentation coefficient of fibrinogen is increased in the presence of heparin and copper ion, compared to the value of fibrinogen-copper systems without heparin, and this effect is enhanced by changing the fibrinogen: heparin molar ratio to larger values. The precipitation of fibrinogen from solution, apparently without a coincident removal of heparin, also increases with increasing copper ion concentration and fibrinogen:heparin molar ratio. The possible significance of these effects in terms of heparin anti-coagulant activity is discussed. * Submitted (by B. L.) in partial fulfillment of the requirements for thePh.D. degree,

Ion-Exchange Resin/Carrageenan-Copper-Based Nanocomposite: Artificial Neural Network, Advanced Thermodynamic Profiling, and Anticoagulant Studies

“…Heparin also interacts with fibrinogen, influencing its polymerization into fibrin strands, which are essential for blood clot formation. 28 The doped Cu 2+ -nickel manganite composite hindered platelet aggregation and interfered with the blood coagulation cascade. 29 Cu 2+ has been found to inhibit several key factors involved in the coagulation process, including thrombin and factor Xa, which are crucial for the conversion of fibrinogen to fibrin, the main component of blood clots.…”

“…Heparin is a well-known anticoagulant that functions by enhancing the activity of antithrombin-III, a natural inhibitor of thrombin and other coagulation factors. Heparin also interacts with fibrinogen, influencing its polymerization into fibrin strands, which are essential for blood clot formation . The doped Cu 2+ -nickel manganite composite hindered platelet aggregation and interfered with the blood coagulation cascade .…”

Influence of Divalent Metal Ions on the Precipitation of the Plasma Protein Fibrinogen

“…Therefore, fibrous fibrinogen scaffolds have become particularly attractive materials to support cell growth in regenerative medicine. , A prerequisite for cell proliferation is the integrin-mediated adhesion to the Arg-Gly-Asp (RGD) binding site of fibrinogen, which is activated by divalent ions including Ca 2+ , Mg 2+ , and Mn 2+ cations . Besides cell signaling, molecular binding of fibrinogen is driven by divalent ions, for instance, the Zn 2+ -dependent interaction of fibrinogen with decorin or the involvement of Cu 2+ ions in the formation of heparin-fibrinogen complexes . Moreover, Cu 2+ ions are involved in wound healing where they stabilize fibrinogen and collagen by activating proangiogenic growth factors, such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) 1 and 2. , The concentration of divalent ions in blood plasma typically varies from 2.2 to 2.7 mM for Ca 2+ , from 0.75 to 1 mM for Mg 2+ , from 16 to 24 μM for Cu 2+ , and from only 10 to 11.5 μM for Zn 2+ …”

“…5 Besides cell signaling, molecular binding of fibrinogen is driven by divalent ions, for instance, the Zn 2+dependent interaction of fibrinogen with decorin 6 or the involvement of Cu 2+ ions in the formation of heparin-fibrinogen complexes. 7 Moreover, Cu 2+ ions are involved in wound healing where they stabilize fibrinogen and collagen by activating proangiogenic growth factors, such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF) 1 and 2. 8,9 The concentration of divalent ions in blood plasma typically varies from 2.2 to 2.7 mM for Ca 2+ , 10 from 0.75 to 1 mM for Mg 2+ , 11 from 16 to 24 μM for Cu 2+ , 12 and from only 10 to 11.5 μM for Zn 2+ .…”