Download PDF
Thromb Haemost 2003; 89(04): 610-621
DOI: 10.1055/s-0037-1613567
Review Article
Schattauer GmbH

Molecular and cellular modulation of fibrinolysis

Krasimir Kolev
1   Department of Medical Biochemistry, Semmelweis University, Budapest, Hungary
,
Raymund Machovich
1   Department of Medical Biochemistry, Semmelweis University, Budapest, Hungary
› Author Affiliations
Further Information

Publication History

Received 30 October 2002

Accepted after revision 10 January 2003

Publication Date:
07 December 2017 (online)

    Permissions and Reprints

Summary

The structure of the fibrin network, the hemodynamic environment of the clot, the kinetic properties of the fibrinolytic enzymes and the balance of their formation and inactivation essentially determine the effectiveness of fibrinolysis in vivo. The fibrin structure and the action of proteases, however depend considerably on additional, apparently inert physiological and pathological factors, which are restricted to more or less transient compartments in fluid-solid interface, such as thrombus (fibrin with platelet membrane structures), endothelial cell surface, the environment of polymorphonuclear cells (PMN). In these compartments extreme changes in concentrations and rate enhancements are observed. Components released by endothelial cells, PMNs and platelets or molecules present in circulating blood create a heterogeneous milieu that modulates fibrinolysis. This review summarizes the effects, and where it is possible, explains the mechanism of modulators of the fibrinolytic processes, such as cell membrane and cellular contents of endothelium, PMN and platelets present in thrombi, the action of normal and pathological blood plasma- and extracellular matrix-components.

Keywords

Compartmental fibrinolysis - fibrin degradation - plasminogen activation - tPA-cofactors - endothelial cells - polymorphonuclear cells
 

  • References

  • 1 Bachmann F. The plasminogen-plasmin enzyme system. In: Hemostasis and Thrombosis.. Colman RW, Hirsh J, Marder VJ, Salzman EW. Eds J. B Lippincott Company; 1994: 1592-622.
    Google Scholar
  • 2 Collen D, Lijnen HR. Basic and clinical aspects of fibrinolysis and thrombolysis. Blood 1991; 78: 3114-24.
    PubMedGoogle Scholar
  • 3 Degen JL. Genetic interactions between the coagulation and fibrinolytic systems. Thromb Haemost 2001; 86: 130-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 4 Ploplis VA, Castellino FJ. Gene targeting of components of the fibrinolytic system. Thromb Haemost 2002; 87: 22-31.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 5 Spraggon G, Everse SJ, Doolittle RF. Crystal structures of fragment D from human fibrinogen and its crosslinked counterpart from fibrin. Nature 1997; 389: 455-62.
    CrossrefPubMedGoogle Scholar
  • 6 Brown JH, Volkmann N, Jun G, Henschen-Edman AH, Cohen C. The crystal structure of modified bovine fibrinogen. Proc Natl Acad Sci USA 2000; 97: 85-90.
    CrossrefPubMedGoogle Scholar
  • 7 Blomback B, Carlsson K, Hessel B, Liljeborg A, Procyk R, Aslund N. Native fibrin gel networks observed by 3D microscopy, permeation and turbidity. Biochim Biophys Acta 1989; 997: 96-110.
    CrossrefPubMedGoogle Scholar
  • 8 Blomback B, Carlsson K, Fatah K, Hessel B, Procyk R. Fibrin in human plasma: gel architecture governed by rate and nature of fibrino-gen activation. Thromb Res 1994; 75: 521-38.
    CrossrefPubMedGoogle Scholar
  • 9 Gruber A, Mori E, del Zoppo GJ, Waxman L, Griffin JH. Alteration of fibrin network by activated protein C. Blood 1994; 83: 2541-8.
    PubMedGoogle Scholar
  • 10 Minton AP. The effect of volume occupancy upon the thermodynamic activity of proteins: some biochemical consequences. Mol Cell Biochem 1983; 55: 119-40.
    CrossrefPubMedGoogle Scholar
  • 11 Rivas G, Fernandez JA, Minton AP. Direct observation of the self-association of dilute proteins in the presence of inert macromolecules at high concentration via tracer sedimentation equilibrium: theory, experiment, and biological significance. Biochemistry 1999; 38: 9379-88.
    CrossrefPubMedGoogle Scholar
  • 12 Torbet J. Fibrin assembly in human plasma and fibrinogen/albumin mixtures. Biochemistry 1986; 25: 5309-14.
    CrossrefPubMedGoogle Scholar
  • 13 Galanakis DK, Lane BP, Simon SR. Albumin modulates lateral assembly of fibrin polymers: evidence of enhanced fine fibril formation and of unique synergism with fibrinogen. Biochemistry 1987; 26: 2389-400.
    CrossrefPubMedGoogle Scholar
  • 14 Coleman M, Vigliano EM, Weksler ME, Nachman RL. Inhibition of fibrin monomer polymerization by lambda myeloma globulins. Blood 1972; 39: 210-23.
    PubMedGoogle Scholar
  • 15 Gabriel DA, Smith LA, Folds JD, Davis L, Cancelosi SE. The influence of immunoglobulin (IgG) on the assembly of fibrin gels. J Lab Clin Med 1983; 1: 545-52.
    PubMedGoogle Scholar
  • 16 Carr ME, Zekert SL. Abnormal clot retraction, altered fibrin structure, and normal platelet function in multiple myeloma. Am J Physiol 1994; 266: H1195-H1201.
    PubMedGoogle Scholar
  • 17 O’Kane MJ, Wisdom GB, Desai ZR, Arch-bold GPR. Inhibition of fibrin monomer polymerisation by myeloma immunoglobulin. J Clin Pathol 1994; 47: 266-8.
    CrossrefPubMedGoogle Scholar
  • 18 Carr ME, Dent RM, Carr SL. Abnormal fibrin structure and inhibition of fibrinolysis in patients with multiple myeloma. J Lab Clin Med 1996; 128: 83-8.
    CrossrefPubMedGoogle Scholar
  • 19 London M. Non-covalent associations of proteins in plasma: self-, mixed fibrin(ogen), mixed protein-non-protein association. Clin Biochem 1997; 30: 83-9.
    CrossrefPubMedGoogle Scholar
  • 20 Gaffney PJ, Whitaker AN. Fibrin crosslinks and lysis rates. Thromb Res 1979; 14: 85-94.
    CrossrefPubMedGoogle Scholar
  • 21 Francis CW, Marder VJ, Martin SE. Plasmic degradation of crosslinked fibrin. I. Structural analysis of the particulate clot and identification of new macromolecular-soluble complexes. Blood 1980; 56: 456-64.
    PubMedGoogle Scholar
  • 22 Siebenlist KR, Mosesson MW. Progressive cross-linking of fibrin γ chains increases resistance to fibrinolysis. J Biol Chem 1994; 269: 28414-9.
    PubMedGoogle Scholar
  • 23 Sakata Y, Aoki N. Crosslinking of α2-plasmin inhibitor to fibrin by fibrin stabilising factor. J Clin Invest 1980; 65: 290-7.
    CrossrefPubMedGoogle Scholar
  • 24 Carr ME, Hardin CL. Fibrin has larger pores when formed in the presence of erythrocytes. Am J Physiol 1987; 253: H1069-H1073.
    PubMedGoogle Scholar
  • 25 Niewiarowski S, Regoeczi E, Stewart GJ, Senyi AF, Mustard JF. Platelet interaction with polymerizing fibrin. J Clin Invest 1972; 51: 685-700.
    CrossrefPubMedGoogle Scholar
  • 26 Carr ME, Carr SL. Fibrin structure and concentration alter clot elastic modulus but do not alter platelet mediated force development. Blood Coagul Fibrinolysis 1995; 6: 79-86.
    CrossrefPubMedGoogle Scholar
  • 27 McBane RD, Ford MAP, Karnicki K, Stewart M, Owen WG. Fibrinogen, fibrin and crosslinking in aging arterial thrombi. Thromb Haemost 2000; 84: 83-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 28 Skarlatos I S, Rao R, Dickens BF, Kruth HS. Phospholipid loss in dying platelets. Virchows Arch 1993; 64: 241-5.
    CrossrefPubMedGoogle Scholar
  • 29 Niewiarowski S, Holt JC, Cook JJ. Biochemistry and physiology of secreted platelet proteins. In: Hemostasis and thrombosis: Basic principles and clinical practice. Colman RW, Hirsh J, Marder VJ, Salzman EW. eds J. B Lippincott Company; 1994: 546-56.
    Google Scholar
  • 30 Schick PK. Megakaryocyte and platelet lipids. In: Hemostasis and thrombosis: Basic principles and clinical practice. Colman RW, Hirsh J, Marder VJ, Salzman EW. eds J. B Lippincott Company; 1994: 574-89.
    Google Scholar
  • 31 Cook BC, Retzinger GS. Lipid microenvironment influences the processivity of adsorbed fibrin(ogen): enzymatic processing and adhesivity of the bound protein. J Coll Interface Sci 1994; 162: 171-81.
    CrossrefPubMedGoogle Scholar
  • 32 Gunther A, Kalinowski M, Elssner A, Seeger W. Clot-embedded natural surfactant: kinetics of fibrinolysis and surface activity. Am J Physiol 1994; 267: L618-L624.
    PubMedGoogle Scholar
  • 33 Retzinger GS, Cook BC, DeAnglis AP. The binding of fibrinogen to surfaces and the identification of two distinct surface-bound species of the protein. J Coll Interface Sci 1994; 168: 514-21.
    CrossrefPubMedGoogle Scholar
  • 34 Retzinger GS. Adsorption and coagulability of fibrinogen on atheromatous lipid surfaces. Arterioscler Thromb Vasc Biol 1995; 15: 786-92.
    CrossrefPubMedGoogle Scholar
  • 35 Cunningham MT, Citron BA, Koerner TAW. Evidence of a phospholipid binding species within human fibrinogen preparations. Thromb Res 1999; 95: 325-34.
    CrossrefPubMedGoogle Scholar
  • 36 Gunther A, Markart P, Kalinowski M, Ruppert C, Grimminger F, Seeger W. Cleavage of surfactant-incorporating fibrin by different fibrinolytic agents. Kinetics of lysis and rescue of surface activity. Am J Resp Cell Mol Biol 1999; 21: 738-45.
    CrossrefPubMedGoogle Scholar
  • 37 Janmey PA, Lind SE, Yin HL, Stossel TP. Effects of semi-dilute actin solutions on the mobility of fibrin protofibrils during clot formation. Biochim Biophys Acta 1985; 841: 151-8.
    CrossrefPubMedGoogle Scholar
  • 38 Kolev K, Tenekedjiev K, Komorowicz E, Machovich R. Functional evaluation of the structural features of proteases and their substrate in fibrin surface degradation. J Biol Chem 1997; 272: 13666-75.
    CrossrefPubMedGoogle Scholar
  • 39 Machovich R, Owen WG. The elastase-mediated pathway of fibrinolysis. Blood Coagul Fibrinolysis 1990; 1: 79-90.
    CrossrefPubMedGoogle Scholar
  • 40 Plow EF, Gramse M, Havemann K. Immunochemical discrimination of leukocyte elastase from plasmic degradation products of fibrinogen. J Lab Clin Med 1983; 102: 858-69.
    PubMedGoogle Scholar
  • 41 Marder VJ, Landskroner K, Novokhatny V, Zimmerman TP, Kong M, Kanouse JJ, Jesmok G. Plasmin induces local thrombolysis without causing hemorrhage: A comparison with tissue plasminogen activator in the rabbit. Thromb Haemost 2001; 80: 739-45.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 42 Kolev K, Komorowicz E, Owen WG, Macho-vich R. Quantitative comparison of fibrin degradation with plasmin, miniplasmin, neutrophil leukocyte elastase and cathepsin G. Thromb Haemost 1996; 75: 140-6.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 43 Ferguson EW, Fretto LJ, McKee PA. A reexamination of the cleavage of fibrinogen and fibrin by plasmin. J Biol Chem 1975; 250: 7210-8.
    PubMedGoogle Scholar
  • 44 Walker JB, Nesheim ME. The molecular weights, mass distribution, chain composition, and structure of soluble fibrin degradation products released from a fibrin clot prefused with plasmin. J Biol Chem 1999; 274: 5201-12.
    CrossrefPubMedGoogle Scholar
  • 45 Collet JP, Park D, Lesty C, Soria J, Soria C, Montalescot G, Weisel JW. Influence of fibrin network conformation and fibrin fiber diameter on fibrinolysis speed. Dynamic and structural approaches by confocal microscopy. Arterioscler Thromb Vasc Biol 2000; 20: 1354-61.
    CrossrefPubMedGoogle Scholar
  • 46 Veklich Y, Francis CW, White J, Weisel JW. Structural studies of fibrinolysis by electron microscopy. Blood 1998; 92: 4721-9.
    PubMedGoogle Scholar
  • 47 Collet JP, Mishal Z, Lesty C, Mirshahi M, Peynet J, Baumelou A, Bensman A, Soria J, Soria C. Abnormal fibrin clot architecture in nephrotic patients is related to hypofibrinoly-sis: influence of plasma biochemical modifications - A possible mechanism for the high thrombotic tendency. Thromb Haemost 1999; 82: 1482-9.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 48 Collet JP, Soria J, Mirshahi M, Hirsh M, Dagonnet FB, Caen J, Soria C. Dusart syndrome: a new concept of the relationship between fibrin clot architecture and fibrin clot degrad-ability: hypofibrinolysis related to an abnormal clot structure. Blood 1992; 82: 2462-9.
    PubMedGoogle Scholar
  • 49 Mills JD, Ariens RAS, Mansfield MW, Grant PJ. Altered fibrin clot structure in the healthy relatives of patients with premature coronary artery disease. Circulation 2002; 106: 1938-42.
    CrossrefPubMedGoogle Scholar
  • 50 Kolev K, Gombás J, Váradi B, Skopál J, Mede K, Pitlil E, Nagy Z, Machovich R. Immun-globulin G from patients with antiphospho-lipid syndrome impairs the fibrin dissolution with plasmin. Thromb Haemost 2002; 87: 502-8.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 51 Gabriel DA, Muga K, Boothroyd EM. The effect of fibrin structure on fibrinolysis. J Biol Chem 1992; 267: 24259-63.
    PubMedGoogle Scholar
  • 52 Binder BR, Christ G, Gruber F, Grubic N, Hufnagl O, Krebs M, Mihály J, Prager GW. Plasminogen activator inhibitor-1: physiological and pathophysiological roles. New Physiol Sci 2002; 17: 56-61.
    PubMedGoogle Scholar
  • 53 Mosher DF, Misenheimer TM, Stenflo J, Hogg PJ. Modulation of fibrinolysis by thrombospondin. Ann NY Acad Sci 1992; 667: 64-9.
    CrossrefPubMedGoogle Scholar
  • 53a Kolev K, Tenekededjier K, Ajtai K, Kovalszky I, Gombàs J, Váradi B, Machovich R. Myosin a non-covalent stabilizer of fibrin in the process of clot dissolution. Blood. 2003: online DOI 10.11.82/blood–2002–10–3227..
    PubMedGoogle Scholar
  • 54 Lind SE, Smith CJ. Actin is a noncompetitive plasmin inhibitor. J Biol Chem 1991; 266: 5273-8.
    PubMedGoogle Scholar
  • 55 Ploplis VA, Carmeliet P, Vazirzadeh S, Van Vlaenderen I, Moons L, Plow EF, Collen D. Effects of disruption of the plasminogen gene on thrombosis, growth, and health in mice. Circulation 1995; 9: 2585-93.
    PubMedGoogle Scholar
  • 56 Bugge TH, Flick MJ, Daugherty CC, Degen JL. Plasminogen deficiency causes severe thrombosis but is compatible with development and reproduction. Genes Dev 1995; 9: 794-807.
    CrossrefPubMedGoogle Scholar
  • 57 Zeng B, Bruce D, Kril J, Ploplis V, Freedman B, Brieger D. Influences of plasminogen deficiency on the contribution of polymorphonu-clear leukocytes to fibrin/ogenolysis. Studies in plasminogen knock-out mice. Thromb Haemost 2002; 88: 805-10.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 58 Imamura T, Kaneda H, Nakamura S. New functions of neutrophils in the Arthus reaction: expression of tissue factor, the clotting initiator, and fibrinolysis by elastase. Lab Invest 2002; 82: 1287-95.
    CrossrefPubMedGoogle Scholar
  • 59 Barnhart I M. Importance of neutrophilic leukocytes in the resolution of fibrin. Fed Proc 1965; 24: 846-53.
    PubMedGoogle Scholar
  • 60 Moroz LA. Nonplasmin-mediated fibrinoly-sis. Semin Thromb Hemost 1984; 10: 80-6.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 61 Hajjar KA, Deora A. New concepts in fibrinolysis and angiogenesis. Curr Atheroscler Rep 2000; 2: 417-21.
    CrossrefPubMedGoogle Scholar
  • 62 Holmes WE, Nelles L, Lijnen HR, Collen D. Primary structure of human α2-antiplasmin, a serine protease inhibitor. J Biol Chem 1987; 262: 1659-64.
    PubMedGoogle Scholar
  • 63 Kolev K, Léránt I, Tenekejiev K, Machovich R. Regulation of fibrinolytic activity of neutrophil leukocyte elastase, plasmin and mini-plasmin by plasma protease inhibitors. J Biol Chem 1994; 269: 17030-4.
    PubMedGoogle Scholar
  • 64 Machovich R, Bauer PI, Arányi P, Kecskés É, Horváth I. Kinetic analysis of heparin-enhanced plasmin-antithrombin III reaction. Apparent catalytic role of heparin. Biochem J 1981; 199: 521-6.
    CrossrefPubMedGoogle Scholar
  • 65 Marshall JM. Brown AJ. Ponting CP. Conformational studies of human plasminogen and plasminogen fragments: evidence for a novel third conformation of plasminogen. Biochemistry 1994; 33: 3599-606.
    CrossrefPubMedGoogle Scholar
  • 66 Cockell CS, Marshall JM, Dawson KM, Cederholm-Williams SA. Ponting CP. Evidence that the conformation of unliganded human plasminogen is maintained via an intramolecular interaction between the lysine-binding site of kringle 5 and the N-terminal peptide. Biochem J 1998; 333: 99-105.
    CrossrefPubMedGoogle Scholar
  • 67 Chibber BAK, Castellino FJ. Regulation of the streptokinase-mediated activation of human plasminogen by fibrinogen and chloride ions. J Biol Chem 1986; 261: 5289-95.
    PubMedGoogle Scholar
  • 68 Machovich R, Owen WG. 6-Aminohexanoate and chloride ion in the activation of porcine plasminogens by urokinase. Biochim Biophys Acta 1990; 1040: 109-11.
    CrossrefPubMedGoogle Scholar
  • 69 Suenson E, Thorsen S. The course and prerequisites of Lys-plasminogen formation during fibrinolysis. Biochemistry 1988; 27: 2435-43.
    CrossrefPubMedGoogle Scholar
  • 70 Machovich R, Litwiller RD, Owen WG. Requirement of zymogen modification for activation of porcine plasminogen. Biochemistry 1992; 31: 11558-61.
    CrossrefPubMedGoogle Scholar
  • 71 Machovich R, Owen WG. Facilitation of plasminogen activation by a plasmin substrate containing a lysyl residue. Thromb Haemost 1993; 70: 864-6.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 72 Kolev K, Owen WG, Machovich R. Dual effect of plasmin substrates on plasminogen activation. Biochim Biophys Acta 1995; 1247: 239-45.
    CrossrefPubMedGoogle Scholar
  • 73 Carmeliet P, Schoonjans L, Kieckens L, Ream B, Degen J, Bronson R, De Vos R, van den Oord JJ, Collen D, Mulligan RC. Physiological consequences of loss of plasminogen activator gene function in mice. Nature 1994; 368: 419-24.
    CrossrefPubMedGoogle Scholar
  • 74 Braat EAM, Dooijewaard G, Rijken DC. Fibrinolytic properties of activated FXII. Eur J Biochem 1999; 263: 904-11.
    CrossrefPubMedGoogle Scholar
  • 75 Reddy KNN. Streptokinase – biochemistry and clinical application. Enzyme 1988; 40: 79-89.
    CrossrefPubMedGoogle Scholar
  • 76 Reed GL, Houng AK, Liu L, Parhami-Seren B, Matsueda LH, Wang S, Hedstrom L. Catalytic switch and the conversion of strep-tokinase to a fibrin-targeted plasminogen activator. Proc Natl Acad Sci USA 1999; 96: 8879-83.
    CrossrefPubMedGoogle Scholar
  • 77 Medved L, Tsurupa G, Yakovlev S. Conformational changes upon conversion of fibrinogen into fibrin: the mechanisms of exposure of cryptic sites. Ann NY Acad Sci 2001; 936: 185-204.
    PubMedGoogle Scholar
  • 78 Thorsen S. The mechanism of plasminogen activation and the variability of the fibrin effector during tissue-type plasminogen activator-mediated fibrinolysis. Ann New York Acad Sci 1992; 667: 52-63.
    CrossrefPubMedGoogle Scholar
  • 79 Nieuwenhuizen W. Fibrin-mediated plasminogen activation. Ann NY Acad Sci 2001; 936: 237-46.
    PubMedGoogle Scholar
  • 80 Nesheim M, Walker J, Wang W, Boffa M, Horrevoets A, Bajzár L. Modulation of fibrin cofactor activity in plasminogen activation. Ann New York Acad Sci 2001; 936: 247-60.
    PubMedGoogle Scholar
  • 81 Wang W, Boffa MB, Bajzár L, Walker JB, Nesheim ME. A study of the mechanism of inhibition of fibrinolysis by activated throm-bin-activable fibrinolysis inhibitor. J Biol Chem 1998; 273: 27176-81.
    CrossrefPubMedGoogle Scholar
  • 82 Hoylaerts M, Rijken DC, Lijnen HR, Collen D. Kinetic of the activation of plasminogen by human tissue plasminogen activator. J Biol Chem 1982; 257: 2912-9.
    PubMedGoogle Scholar
  • 83 Stack S, Gonzalez-Gronow M, Pizzo SV. Regulation of plasminogen activation by components of the extracellular matrix. Biochemistry 1990; 29: 4966-70.
    CrossrefPubMedGoogle Scholar
  • 84 Machovich R, Ajtai K, Kolev K, Owen WG. Myosin as cofactor and substrate in fibrinoly-sis. FEBS Lett 1997; 407: 93-6.
    CrossrefPubMedGoogle Scholar
  • 85 Lind SE, Smith CF. Actin accelerates plasmin generation by tissue plasminogen activator. J Biol Chem 1991; 266: 17673-8.
    PubMedGoogle Scholar
  • 86 Allen RA. An enhancing effect of poly-lysine on the activation of plasminogen. Thromb Haemost 1982; 47: 41-5.
    PubMedGoogle Scholar
  • 87 Pryzdial E, Bajzár L, Nesheim ME. Prothrombinase components can accelerate tissue plasminogen activator-catalyzed plasminogen activation. J Biol Chem 1995; 270: 17871-7.
    CrossrefPubMedGoogle Scholar
  • 88 Pryzdial EL, Lavigne N, Dupuis N, Kessler GE. Plasmin converts factor X from coagulation zymogen to fibrinolysis cofactor. J Biol Chem 1999; 274: 8500-5.
    CrossrefPubMedGoogle Scholar
  • 89 Radcliffe R, Heinze T. Stimulation of tissue plasminogen activator by denatured proteins and fibrin clots: A possible additional role for plasminogen activator. Arch Biochem Biophys 1981; 211: 750-61.
    CrossrefPubMedGoogle Scholar
  • 90 Machovich R, Owen WG. Denatured proteins as cofactors for plasminogen activation. Arch Biochem Biophys 1997; 344: 343-9.
    CrossrefPubMedGoogle Scholar
  • 91 Machovich R, Komorowicz E, Kolev K, Owen WG. Facilitation of plasminogen activation by denatured prothrombin. Thromb Res 1999; 94: 389-94.
    CrossrefPubMedGoogle Scholar
  • 92 Arza B, Hoylaerts MF, Felez J, Collen D, Lijnen HR. Prostomelysin-1 (proMMP-3) stimulates plasminogen activation by tissue-type plasminogen activator. Eur J Biochem 2000; 267: 6378-84.
    CrossrefPubMedGoogle Scholar
  • 93 Hajjar KA, Nachman I R. Endothelial cell-mediated conversion of Glu-plasminogen to Lys-plasminogen. Further evidence for assembly of the fibrinolytic system on the endothelial cell surface. J Clin Invest 1988; 82: 1769-78.
    CrossrefPubMedGoogle Scholar
  • 94 Machovich R, Owen WG. A factor from endothelium facilitates activation of plasminogen by tissue plasminogen activator. Enzyme 1988; 40: 109-12.
    CrossrefPubMedGoogle Scholar
  • 95 Gong Y, Kim S, Felez J, Grella DK, Castellino FJ, Miles LA. Conversion of Glu-plasmino-gen to Lys-plasminogen is necessary for optimal stimulation of plasminogen activation on the endothelial cell surface. J Biol. Chem 2001; 276: 19078-83.
    PubMedGoogle Scholar
  • 96 Utermann G. The mysteries of lipoprotein(a). Science 1989; 246: 904-10.
    CrossrefPubMedGoogle Scholar
  • 97 Zenker G, Koltringer P, Bone G, Niedorkorn K, Pfiffer K, Jurgen G. Lipoprotein(a) as a strong indicator for cerebrovascular disease. Stroke 1989; 17: 942-5.
    PubMedGoogle Scholar
  • 98 Lucas MA, Fretto LJ, McKee PA. The binding of human plasminogen to fibrin and fibrino-gen. J Biol Chem 1983; 258: 4249-56.
    PubMedGoogle Scholar
  • 99 Weisel JW, Nagaswami C, Korsholm B, Petersen LC, Suenson E. Interactions of plasminogen with polymerizing fibrin and its derivatives, monitored with a photoaffinity cross-linker and electron microscopy. J Mol Biol 1994; 235: 1117-35.
    CrossrefPubMedGoogle Scholar
  • 100 Harpel PC, Borth W. Fibrin, lipoprotein(a), plasmin interactions: A model linking thrombosis and atherogenesis. Ann NY Acad Sci 1992; 667: 233-8.
    CrossrefPubMedGoogle Scholar
  • 101 Nachman RL. Thrombosis and atherogenesis: molecular connections. Blood 1992; 79: 1897-906.
    PubMedGoogle Scholar
  • 102 Ling Q, Hajjar KA. Inhibition of endothelial cell thromboresistance by homocysteine. J Nutr 2000; 130: 373S-376S.
    CrossrefPubMedGoogle Scholar
  • 103 Léránt I, Kolev K, Gombás J, Machovich R. Modulation of plasminogen activation and plasmin activity by methylglyoxal modification of the zymogen. Biochim Biophys Acta 2000; 1480: 311-20.
    CrossrefPubMedGoogle Scholar
  • 104 Preissner K, Nawroth PP, Kanse SM. Vascular protease receptors: integrating haemostasis and endothelial cell functions. J Pathol 2000; 190: 360-72.
    CrossrefPubMedGoogle Scholar
  • 105 Hajjar KA. Changing concepts in fibrinolysis. Curr Opinion Hematol 1995; 2: 345-50.
    CrossrefPubMedGoogle Scholar
  • 106 Bauer I P, Machovich R, Büki KG, Csonka E, Koch S, Horváth I. Interaction of plasmin with endothelial cells. Biochem J 1984; 218: 119-24.
    CrossrefPubMedGoogle Scholar
  • 107 Hajjar KA. The endothelial cell tissue plasminogen activator receptor. J Biol Chem 1991; 266: 21962-70.
    PubMedGoogle Scholar
  • 108 Nagy Z, Kolev K, Pék M, Csonka É, Machovich R. Contraction of human brain endothelial cells induced by thrombogenic and fibrinolytic factors. Stroke 1995; 26: 265-70.
    CrossrefPubMedGoogle Scholar
  • 109 Nagy Z, Kolev K, Csonka É, Vastag M, Machovich R. Perturbation of the integrity of the blood-brain barrier by fibrinolytic enzymes. Blood Coag Fibrinol 1998; 9: 471-8.
    CrossrefPubMedGoogle Scholar
  • 110 Bartha K, Dömötör E, Lanza F, Ádám-Vizi V, Machovich R. Identification of thrombin receptors in rat brain capillary endothelial cells. J Cerebr Blood Flow Metabol 2000; 20: 175-82.
    CrossrefPubMedGoogle Scholar
  • 111 Dömötör E, Bartha K, Machovich R, Ádám-Vizi V. Protease-activated receptor-2 (PAR-2) in brain microvascular endothelium and its regulation by plasmin and elastase. J Neurochem 2002; 80: 746-54.
    CrossrefPubMedGoogle Scholar
  • 112 Sottrup-Jensen L, Claeys H, Zagdel M, Peterson TE, Magnusson S. The primary structure of human plasminogen: isolation of two lysine-binding fragments and one mini-plasminogen by elastase-catalyzed specific limited proteolysis. In: Progress in Chemical Fibrinolysis and Thrombolysis. Davidson JF, Rowan RM, Samama MM, Desnoyers PC. eds Raven Press; 1978. Vol III: 191-209.
    Google Scholar
  • 113 Folkman J. Angiogenesis in cancer, vascular-, rheumatoid and other disease. Nature Med 1995; 1: 27-31.
    CrossrefPubMedGoogle Scholar
  • 114 Machovich R, Owen WG. An elastase-dependent pathway of plasminogen activation. Biochemistry 1989; 28: 4517-22.
    CrossrefPubMedGoogle Scholar
  • 115 Potempa J, Korzus E, Travis J. The serpin superfamily of proteinase inhibitors: structure, function, and regulation. J Biol Chem 1994; 269: 15957-60.
    PubMedGoogle Scholar
  • 116 Baradet TC, Haselgrove JC, Weisel JW. Three-dimensional reconstruction of fibrin clot networks from stereoscopic intermediate voltage electron microscope images and analysis of branching. Biophys J 1995; 68: 1551-60.
    CrossrefPubMedGoogle Scholar
  • 117 Matveyev MY, Domogatsky SP. Penetration of macromolecules into contracted blood clots. Biophys J 1992; 63: 862-3.
    CrossrefPubMedGoogle Scholar
  • 118 Blinc A, Planinsic G, Keber D, Jarh O, Lahajnar G, Zidansek A, Demsar F. Dependence of blood clot lysis on the mode of transport of urokinase into the clot – a magnetic resonance imaging study in vitro. Thromb Haemost 1991; 65: 549-52.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 119 Diamond SL, Anand S. Inner clot diffusion and permeation during fibrinolysis. Biophys J 1993; 65: 2622-43.
    CrossrefPubMedGoogle Scholar
  • 120 Wu JH, Siddiqui K, Diamond SL. Transport phenomena and clot dissolving therapy: an experimental investigation of diffusion-controlled and permeation-enhanced fibrinolysis. Thromb Haemost 1994; 72: 105-12.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 121 Sakharov DV, Rijken DC. Superficial accumulation of plasminogen during plasma clot lysis. Circulation 1995; 92: 1883-90.
    CrossrefPubMedGoogle Scholar
  • 122 Anand S, Wu JH, Diamond SL. Enzyme-mediated proteolysis of fibrous biopolymers: dissolution front movement in fibrin or collagen under conditions of diffusive or convective transport. Biotechnol Bioengin 1995; 48: 89-107.
    CrossrefPubMedGoogle Scholar
  • 123 Komorowicz E, Kolev K, Léránt I, Machovich R. Flow rate-modulated dissolution of fibrin with clot-embedded and circulating proteases. Circ Res 1998; 82: 1102-8.
    CrossrefPubMedGoogle Scholar
  • 124 Plow EF, Felez J, Miles LA. Cellular regulation of fibrinolysis. Thromb Haemost 1991; 66: 32-6.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 125 Hall SV, Humphries JE, Gonias SL. Inhibition of cell surface receptor-bound plasmin by α2-antiplasmin and α2-macroglobulin. J Biol Chem 1991; 266: 12329-36.
    PubMedGoogle Scholar
  • 126 Machovich R. Kinetic parameters for plasminogen activation by tissue type plasmino-gen activator. Thromb Haemost 1997; 77: 1041-2.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 127 Sinninger V, Merton RE, Fabregas P, Felez J, Longstaff C. Regulation of tissue plasmino-gen activator activity by cells – domains responsible for binding and mechanism of stimulation. J Biol Chem 1999; 274: 12414-22.
    CrossrefPubMedGoogle Scholar
  • 128 Longstaff C. Plasminogen activation on the cell surface. Front Biosci 2002; 7: D244-D255.
    CrossrefPubMedGoogle Scholar
  • 129 Felez J, Miles LA, Fábregas P, Jardi M, Plow EF, Lijnen RH. Characterization of cellular binding sites and interactive regions within reactants required for enhancement of plasminogen activation by tPA on the surface of leukocytic cells. Thromb Haemost 1996; 76: 577-84.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 130 Herren T, Burke TA, Jardi M, Felez J, Plow EF. Regulation of plasminogen binding to neutrophils. Blood 2001; 97: 1070-8.
    CrossrefPubMedGoogle Scholar
  • 131 Loike JD, Silverstein R, Wright SD, Weitz I J, Huang AJ, Silverstein SC. The role of protected extracellular compartments in interactions between leukocytes and platelets and fibrin/fibrinogen matrices. Ann NY Acad Sci 1994; 667: 163-72.
    PubMedGoogle Scholar
  • 132 Liou TG, Campbell EJ. Nonisotropic enzyme-inhibitor interactions: a novel nonoxidative mechanism for quantum proteolysis by human neutrophils. Biochemistry 1995; 34: 16171-7.
    CrossrefPubMedGoogle Scholar
  • 133 Liou TG, Campbell EJ. Quantum proteolysis resulting from release of single granules by human neutrophils. A novel, nonoxidative mechanism of extracellular proteolytic activity. J Immunol 1996; 157: 2624-31.
    PubMedGoogle Scholar
  • 134 Ugarova TP, Yakubenko VP. Recognition of fibrinogen by leukocyte integrins. Ann NY Acad Sci 2001; 936: 368-85.
    PubMedGoogle Scholar
  • 135 Charo IF, Bekeart LS, Philips DR. Platelet glycoprotein IIb-IIIa-like proteins mediate endothelial cell attachment to adhesive proteins and the extracellular matrix. J Biol Chem 1987; 262: 9935-8.
    PubMedGoogle Scholar
  • 136 Suehiro K, Gailit J, Plow EF. Fibrinogen is a ligand for integrin α5β1on endothelial cells. J Biol Chem 1997; 272: 5360-6.
    CrossrefPubMedGoogle Scholar
  • 137 Languino LR, Plescia J, Duperray A, Brian AA, Plow EF, Geltosky JE, Altieri DC. Fibrinogen mediates leukocyte adhesion to vascular endothelium through an ICAM-1-dependent pathway. Cell 1993; 73: 1423-34.
    CrossrefPubMedGoogle Scholar
  • 138 Languino LR, Duperray A, Joganic KJ, For-naro M, Thornton GB, Altieri DC. Regulation of leukocyte-endothelium interaction and leukocyte transendothelial migration by inter-cellular-adhesion molecule 1 – fibrinogen recognition. Proc Natl Acas Sci USA 1995; 92: 1505-9.
    CrossrefPubMedGoogle Scholar
  • 139 Martinez J, Rich E, Barsigian C. Trans-glutaminase-mediated cross-linking of fibrinogen by human umbilical vein endothelial cells. J Biol Chem 1989; 264: 20502-8.
    PubMedGoogle Scholar