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• W2044595268 abstract "Molecular assembly of plasminogen and tissue-type plasminogen activator (t-PA) at the surface of fibrin results in the generation of fibrin-bound plasmin and thereby in the dissolution of a clot. This mechanism is triggered by specific interactions of intra-chain surface lysine residues in fibrin with the kringle domains of plasminogen, and is further amplified via the interaction of plasminogen kringles with the carboxy-terminal lysine residues of fibrin that are exposed by plasmin cleavage. By virtue of its marked homology with plasminogen, apo(a), the specific apolipoprotein component of Lp(a), may bind to the lysine sites available for plasminogen on the surface of fibrin and thereby interfere with the fibrinolytic process. A sensitive solid-phase fibrin system, which allows the study of plasminogen activation at the plasma fibrin interface and makes feasible the analysis of products bound to fibrin, has been used to investigate the effects of Lp(a) on the binding of plasminogen and its activation by fibrin-bound t-PA. Plasma samples from human subjects with high levels of Lp(a) were studied. We have established that Lp(a) binds to the fibrin surface and thereby competes with plasminogen (Ki = 44 nM) so as to inhibit its activation. We have further shown that Lp(a) blocks specifically carboxy-terminal lysine residues on the surface of fibrin. To further explore the role of apo(a) on the Lp(a) fibrin interactions, we have performed ligand-binding studies using a recombinant form of apo(a) that contains 17 kringle 4-like units. We have shown that recombinant apo(a) binds specifically to fibrin (Kd = 26 +/- 8 nM, Bmax = 26 +/- 2 fmol/well) and that this binding increases upon treatment of the fibrin surface with plasmin (Kd = 8 +/- 4 nM, Bmax = 115 +/- 14 fmol/well). Altogether, our results indicate clearly that binding of native Lp(a) through this mechanism may impair clot lysis and may favor the accumulation of cholesterol in thrombi at sites of vascular injury." @default.
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• W2044595268 date "1994-01-01" @default.
• W2044595268 modified "2023-10-16" @default.
• W2044595268 title "Effects of lipoprotein(a) on the binding of plasminogen to fibrin and its activation by fibrin-bound tissue-type plasminogen activator" @default.
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• W2044595268 doi "https://doi.org/10.1016/0009-3084(94)90159-7" @default.
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• W2044595268 hasPublicationYear "1994" @default.
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