Ukr.Biochem.J. 2016; Volume 88, Issue 2, Mar-Apr, pp. 16-24

doi: https://doi.org/10.15407/ubj88.02.016

Effect of fibrin degradation products on fibrinolytic process

T. A. Yatsenko, V. М. Rybachuk, O. I. Yusova, S. M. Kharchenko, T. V. Grinenko

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: topolius@yandex.ua

Fibrin clot lysis by plasminogen/plasmin system results in fibrin degradation products formation with subsequent release into bloodstream. The fragments contain specific binding sites for fibrinolytic system components and can interact with them. In this study, we investigated the way in which fibrin fragments effect fibrinolytic process. We have shown that high molecular weight products of fibrin degradation and fibrin fragments of DDE-complex and DD, but not end product Е3, stimulate plasmin formation. Additionally, components of DDE-complex mixture of fragments Е1 and Е2 have potentiation ability. The intermediate fibrin fragments hmFDPs and DDE attenuate clot lysis by plasmin and hmFDPs protect plasmin from α2-antiplasmin inhibition but under further fragmentation to endpoint fibrin fragments loose this ability. The plasma inhibitors reduce fibrinolytic system activity generated by the degradation products. Thus, fibrin fragments formed during the clot lysis can bind and move out fibrinolytic system components from clot volume and in this way result in clot resistance to hydrolysis.

Keywords: , , , , ,


References:

  1. Aisina RB, Mukhametova LI. Structure and functions of plasminogen/plasmin system. Bioorg Khim. 2014 Nov-Dec;40(6):642-57. Russian. PubMed, CrossRef
  2. Yakovlev S, Makogonenko E, Kurochkina N, Nieuwenhuizen W, Ingham K, Medved L. Conversion of fibrinogen to fibrin: mechanism of exposure of tPA- and plasminogen-binding sites. Biochemistry. 2000 Dec 26;39(51):15730-41. PubMedCrossRef
  3. Lugovskoy EV, Makogonenko EM, Komissarenko SV. Molecular mechanisms of formation and degradation of fibrin. Physical, chemical and immunochemical analysis. K.: Naukova Dumka, 2013. 230 p. (In Russian).
  4. Schuliga M. The inflammatory actions of coagulant and fibrinolytic proteases in disease. Mediators Inflamm. 2015;2015:437695.  PubMed, PubMedCentralCrossRef
  5. Weitz JI, Leslie B, Ginsberg J. Soluble fibrin degradation products potentiate tissue plasminogen activator-induced fibrinogen proteolysis. J Clin Invest. 1991 Mar;87(3):1082-90. PubMed, PubMedCentral, CrossRef
  6. Stewart RJ, Fredenburgh JC, Weitz JI. Characterization of the interactions of plasminogen and tissue and vampire bat plasminogen activators with fibrinogen, fibrin, and the complex of D-dimer noncovalently linked to fragment E. J Biol Chem. 1998 Jul 17;273(29):18292-9. PubMedCrossRef
  7. Robson SC, Shephard EG, Kirsch RE. Fibrin degradation product D-dimer induces the synthesis and release of biologically active IL-1 beta, IL-6 and plasminogen activator inhibitors from monocytes in vitro. Br J Haematol. 1994 Feb;86(2):322-6. PubMed, CrossRef
  8. Naito M, Stirk CM, Smith EB, Thompson WD. Smooth muscle cell outgrowth stimulated by fibrin degradation products. The potential role of fibrin fragment E in restenosis and atherogenesis. Thromb Res. 2000 Apr 15;98(2):165-74. PubMed, CrossRef
  9. Jennewein C, Tran N, Paulus P, Ellinghaus P, Eble JA, Zacharowski K. Novel aspects of fibrin(ogen) fragments during inflammation. Mol Med. 2011 May-Jun;17(5-6):568-73. PubMed, PubMedCentral, CrossRef
  10. Varetska TV. Microgeterogenety of fibrinogen. Cryofibrinogen. Ukr Biokhim Zhurn. 1960;32(1):13-24.
  11. Deutsch DG, Mertz ET. Plasminogen: purification from human plasma by affinity chromatography. Science. 1970 Dec 4;170(3962):1095-6. PubMed, CrossRef
  12. Pozdnjakova TM, Musjalkovskaja AA, Ugarova TP, Protvin DD, Kotsjuruba VN. On the properties of fibrin monomer prepared from fibrin clot with acetic acid. Thromb Res. 1979;16(1-2):283-8. PubMedCrossRef
  13. Belitser VA, Platonova TN, Musialkovskaia AA. Inhibition of fibrin monomer polymerization by fibrinolysis products–fragments D and DD. Dokl Akad Nauk SSSR. 1986;291(4):1001-4. Russian. PubMed
  14. Olexa SA, Budzynski AZ. Primary soluble plasmic degradation product of human cross-linked fibrin. Isolation and stoichiometry of the (DD)E complex. Biochemistry. 1979 Mar 20;18(6):991-5. PubMed, CrossRef
  15. Ugarova TP, Budzynski AZ. Interaction between complementary polymerization sites in the structural D and E domains of human fibrin. J Biol Chem. 1992 Jul 5;267(19):13687-93. PubMed
  16. Bouvier S.A., Beretta-Piccoli M., Giacometti N. Light scattering measurements of polimerization and depolimerization of fibrin: a tool for studing coagulation and fibrinolysis. Progress in chemical fibrinolysis and thrombolysis. Eds. Davidson J.F. et al. N.Y.: Raven Press. 1975; 1: 281-288.
  17. Nieuwenhuizen W. Fibrin-mediated plasminogen activation. Ann N Y Acad Sci. 2001;936:237-46. PubMedCrossRef
  18. Medved L, Tsurupa G, Yakovlev S. Conformational changes upon conversion of fibrinogen into fibrin. The mechanisms of exposure of cryptic sites. Ann N Y Acad Sci. 2001;936:185-204. PubMed, CrossRef
  19. Hasan AA, Chang WS, Budzynski AZ. Binding of fibrin fragments to one-chain and two-chain tissue-type plasminogen activator. Blood. 1992 May 1;79(9):2313-21. PubMed
  20. Skomorovskaya EV, Grinenko TV, Platonova TN. Interaction between Glu-plasminogen and Lys-plasminogen with DH-dimer. / Abstract book of the XVth Congress of International Society on thrombosis and haemostasis. Jerusalem, Israel. 1995.
  21. Olexa SA, Budzynski AZ, Doolittle RF, Cottrell BA, Greene TC. Structure of fragment E species from human cross-linked fibrin. Biochemistry. 1981 Oct 13;20(21):6139-45.   PubMed, CrossRef
  22. Stewart RJ, Fredenburgh JC, Rischke JA, Bajzar L, Weitz JI. Thrombin-activable fibrinolysis inhibitor attenuates (DD)E-mediated stimulation of plasminogen activation by reducing the affinity of (DD)E for tissue plasminogen activator. A potential mechanism for enhancing the fibrin specificity of tissue plasminogen activator. J Biol Chem. 2000 Nov 24;275(47):36612-20. PubMedCrossRef
  23. Yatsenko T, Rybachuk VN, Kharchenko SM, Grinenko TV, Yusova EI. Effect of fribrinigen degradation products on various stages of the fibrinolytic process.  J Pre-Clin Clin Res. 2015 Jun 18;9(1):18-22. CrossRef

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License.