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Thromb Haemost 1995; 74(01): 493-498
DOI: 10.1055/s-0038-1642727
Symposium
Thrombin as a Target of Antithrombotic Therapy
Schattauer GmbH Stuttgart

Thrombin Functions and Antithrombotic Intervention

John W Fenton II
New York State Department of Health, Wadsworth Center for Laboratories and Research; and Departments of Physiology and Cell Biology and Biochemistry and Molecular Biology, Albany Medical College, Albany, NY, USA
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Publication History

Publication Date:
09 July 2018 (online)

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  • References

  • 1 Fenton II JW, Fasco MJ, Stackrow AB, Aronson DL, Young AM, Finlay son JS. Human thrombins. Production, evaluation, and properties of cx-thrombin. J Biol Chem 1977; 252: 3587-3598
    PubMedGoogle Scholar
  • 2 Fenton II JW, Landis BH, Walz DA, Finlayson JS. In: Chemistry and Biology of Thrombin. Lundblad RL, Fenton II JW, Mann KG. (eds) Ann Arbor Science Publishers; Ann Arbor: 1977. pp 43-70
  • 3 Fenton II JW. Thrombin specificity. Ann NY Acad Sci 1981; 370: 468-495
    CrossrefPubMedGoogle Scholar
  • 4 Fenton II JW. Thrombin. Ann NY Acad Sci 1986; 485: 5-15
    CrossrefPubMedGoogle Scholar
  • 5 Fenton II JW. Thrombin bioregulatory functions. Adv Clin Enzymol 1988; 6: 186-193
    PubMedGoogle Scholar
  • 6 Fenton II JW. Regulation of thrombin generation and functions. Semin Thromb Hemost 1988; 14: 234-240
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Fenton II JW, Ofosu FA, Moon DG, Maraganore JM. Thrombin structure and function: why thrombin is the primary target for antithrombotics. Blood Coagul Fibrinolys 1991; 2: 69-75
    PubMedGoogle Scholar
  • 8 Fenton II JW, Ofosu FA, Brezniak DV, Hassouna HI. Understanding thrombin and hemostasis. Hematol/Oncol Clin N Am 1993; 7: 1107-1119
    CrossrefPubMedGoogle Scholar
  • 9 Stubbs MT, Bode W. A player of many parts: the spotlight falls on thrombin’s structure. Thromb Res 1993; 69: 1-58
    CrossrefPubMedGoogle Scholar
  • 10 Irwin DM, Robertson KA, MacGillivray TA. Structure and evolution of the bovine prothrombin gene. J Mol Biol 1988; 200: 31-45
    CrossrefPubMedGoogle Scholar
  • 11 Iwanaga S, Miyata T, Tokunaga F, Muta T. Molecular mechanism of hemolymph clotting system in limulus. Thromb Res 1992; 68: 1-32
    PubMedGoogle Scholar
  • 12 Vu T-KH, Hung DT, Wheaton VI, Coughlin SR. Molecular cloning of a functional thrombin receptor reveals a novel proteolytic mechanism of receptor activation. Cell 1991; 64: 1057-1068
    CrossrefPubMedGoogle Scholar
  • 13 Rasmussen UB, Vouret-Craviari V, Jallot S, Schlesinger Y, Pages G, Parirani A, Lecocq J-P, Pouyssegur J, Van Obberghen-Schilling E. DNA cloning and expression of a hamster a-thrombin receptor coupled to Ca2+ mobilization. FEBS Lett 1991; 288: 123-128
    CrossrefPubMedGoogle Scholar
  • 14 Zhong C-H, Hayzer DA, Corson MA, Runge MS. Molecular cloning of the rat vascular smooth muscle thrombin receptor: evidence for in vitro regulation by basic fibroblast growth factor. J Biol Chem 1992; 267: 16975-16979
    PubMedGoogle Scholar
  • 15 Natarjan S, Riexinger D, Peluso M, Seiler SM. “Tethered ligand” derived pentapeptide agonists of thrombin receptor: a study of side chain requirements for human platelet activation and GTPase stimulation. Int J Peptide Protein Res 1994; 6: 1-7
    PubMedGoogle Scholar
  • 16 Ogletree ML, Natarajan S, Seiler SM. Thrombin receptors as drug discovery targets. Persp Drug Disc Design 1994; 1: 527-536
    PubMedGoogle Scholar
  • 17 Soifer SJ, Peters KG, O’Keefe J, Coughlin ST. Disparate temporal expression of the prothrombin and thrombin receptor genes during mouse development. Am J Pathol 1994; 144: 60-69
    PubMedGoogle Scholar
  • 18 Ofosu FA, Hirsh J, Esmon CT, Modi GJ, Smith LM, Anvari N, Buchanan MR, Fenton II JW, Blajchman MA. Unfractionated heparin inhibits thrombin-catalyzed amplification reactions of coagulation more efficiently than those catalyzed by factor Xa. Biochem J 1989; 257: 143-150
    CrossrefPubMedGoogle Scholar
  • 19 Yang SJ, Blajchman MA, Graven S, Smith LM, Anvari N, Ofosu FA. Activation of factor V during intrinsic and extrinsic coagulation. Inhibition by heparin, hirudin and D-Phe-Pro-Arg-CHsCl. Biochem J 1990; 272: 399-406
    CrossrefPubMedGoogle Scholar
  • 20 Ofosu FA, Fenton II JW, Maraganore JM, Blajchman MA, Yang X, Smith L, Anvari N, Buchanan MR, Hirsh J. Inhibition of the amplification reaction of blood coagulation by site-specific inhibitors of cx-thrombin. Biochem J 1992; 283: 893-897
    CrossrefPubMedGoogle Scholar
  • 21 Bing DH, Laura R, Robison DJ, Furie B, Furie BC, Feldmann RJ. A computer-generated three-dimensional model of the B chain of bovine cx-thrombin. Ann NY Acad Sci 1981; 370: 496-510
    CrossrefPubMedGoogle Scholar
  • 22 Fenton II JW, Bing DH. Thrombin active-site regions. Semin Thromb Hemost 1986; 12: 200-220
    Article in Thieme ConnectPubMedGoogle Scholar
  • 23 Bode W, Mayr I, Baumann V, Huber R, Stone SR, Hofsteenge J. The refined 1.9 A crystal structure of human cx-thrombin: interaction with D-Phe-Pro- Arg chloromethyl ketone and significance of the Tyr-Pro-Pro-Trp insertion segment. EMBO J 1989; 8: 3467-3475
    CrossrefPubMedGoogle Scholar
  • 24 Witting JI, Bourdon P, Brezniak DV, Maraganore JM, Fenton II JW. Thrombin specific inhibition by and slow cleavage of hirulog-1. BiochemI 1992; 283: 737-743
    PubMedGoogle Scholar
  • 25 Witting JI, Bourdon P, Maraganore JM, Fenton II JW. Hirulog-1 and -B2 thrombin specificity. Biochem J 1992; 287: 663-664
    CrossrefPubMedGoogle Scholar
  • 26 Wilner GD, Danitz MP, Mudd SM, Hsieh KH, Fenton II JW. Selective immobilization of a-thrombin by surface-bound fibrin. J Lab Clin Med 1981; 97: 403-411
    PubMedGoogle Scholar
  • 27 Lincoff AM, Popma JJ, Ellis SG, Hacker TA, Topol Ej. Abrupt vessel closure complicating coronary angioplasty, clinical angiographic therapeutic. J Am Coll Cardol 1992; 19: 926-933
    CrossrefPubMedGoogle Scholar
  • 28 Liu L, Dewar L, Song Y, Kulczcky M, Blajchman MA, Fenton II JW, Andrew M, Delorme M, Ginsberg J, Preissner KT, Ofosu FA. Inhibition of thrombin by antithrombin III and heparin cofactor II in vivo. Thromb Haemost. 1995 in press
    PubMedGoogle Scholar
  • 29 Weitz JJ, Hudoba M, Massel D, Maraganore J, Hirsch J. Clot- bound thrombin is protected from inactivation by heparin-antithrom- bin III but is susceptible to inactivation by antithrombin Ill-indepen- dent inhibitors. J Clin Invest 1990; 86: 385-391
    CrossrefPubMedGoogle Scholar
  • 30 Bittl JBittl. Hirulog during PTCA for post-infarction and unstable angina. George Washington University 10th International Workshop on Thrombolysis and Interventional Therapy in Acute Myocardial Infarction 13.11.1994. Dallas, TX:
    Google Scholar
  • 31 Fenton II JW. Leeches to hirulogs and other thrombin-directed antithrombotics. Hematol/Oncol Clin North Am 1992; 6: 1121-1129
    CrossrefPubMedGoogle Scholar
  • 32 Fenton II JW, Olson TA, Zabinski MP, Wilner DG. Anion-binding exosite of human a-thrombin and fibrin(ogen) recognition. Biochemistry 1988; 27: 7106-7112
    CrossrefPubMedGoogle Scholar
  • 33 Malik AB, Fenton II JW. Thrombin-mediated increase in vascular endothelial permeability. Semin Thromb Hemost 1992; 18: 193-199
    Article in Thieme ConnectPubMedGoogle Scholar
  • 34 Brezniak DV, Brower MS, Witting JI, Walz DA, Fenton II JW. Human α to ζ-thrombin cleavage occurs with neutrophil cathepsin G or chymotrypsin while fibrinogen clotting activity is retained. Biochemistry 1990; 29: 3536-3542
    CrossrefPubMedGoogle Scholar
  • 35 Bar-Shavit R, Sabbah V, Lampugnani MG, Marchisio PC, Fenton II JW, Vlodavsky I, Dejane E. An Arg-Gly-Asp sequence within thrombin promotes endothelial cell adhesion. J Cell Biol 1991; 112: 335-344
    CrossrefPubMedGoogle Scholar
  • 36 Carney DH, Mann R, Redin WR, Pernia SD, Berry D, Heggers JP, Hayward PG, Robson MC, Christie J, Annabli C, Fenton II JW, Glenn KC. Enhancement of incisional wound healing and neovascularization in normal rats by thrombin and synthetic thrombin receptor-activating peptides. J Clin Invest 1992; 89: 1469-1477
    CrossrefPubMedGoogle Scholar
  • 37 Garcia JG N, Siflinger-Birnboim A, Bizios R, Del Vecchio PJ, Fenton II JW, Malik AB. Thrombin-induced increases in an albumin transport across cultured endothelial monolayers. J Cell Physiol 1986; 128: 96-104
    CrossrefPubMedGoogle Scholar
  • 38 Fenton II JW, Ofosu FA. Thrombin-mediated events implicated in post-thrombotic recovery. In Angiogenesis: Molecular Biology, Clinical Aspects. Maragoudakis ME. (ed) Plenum Press; New York: 1994. pp 253-263
    Google Scholar
  • 39 McNamara CA, Sarembock IJ, Gimple LW, Fenton II JW, Coughlin SR, Owens GK. Thrombin stimulates proliferation of cultured rat aortic smooth muscle cells by a proteolytically activated receptor. J Clin Invest 1993; 91: 91-98
    PubMedGoogle Scholar
  • 40 Nellsen NA, Soifer SJ, O’Keefe J, Vu TK, Charo IF, Coughlin SR. Thrombin receptor expression in normal and atherosclerotic human arteries. J Clin Invest 1992; 90: 1614-1621
    CrossrefPubMedGoogle Scholar
  • 41 Wilcox JN, Rodriquez J, Subramanian R, Ollerenshaw J, Zhong C, Jayer DH, Horaist C, Hanson SR, Lumsden A, Salam TA, Kelly AB, Harker LA, Runge M. Characterization of thrombin receptor expression during vascular lesion formation. Circ Res 1994; 75: 1029-1038
    CrossrefPubMedGoogle Scholar
  • 42 Sarembock IJ, Gertz SD, Gimple LW, Owen RM, Powers ER, Roberts WC. Effectiveness of recombinant desulphatohirudin (CGP 39393) in reducing restenosis after balloon angioplasty of atherosclerotic femoral arteries in rabbits. Circulation 1991; 84: 232-243
    CrossrefPubMedGoogle Scholar
  • 43 Levin EG, Stern DM, Nawroth PP, Marlar RA, Fair DS, Fenton II JW, Harker LA. Specificity of the thrombin-induced release of tissue plasminogen activator from cultured human endothelial cells. Thromb Haemost 1986; 56: 115-119
    Article in Thieme ConnectPubMedGoogle Scholar
  • 44 Catalfamo JL, Ander TT, Fenton II JW. Thrombin receptoractivating peptides unlike thrombin are insufficient for platelet activation in most species. Thromb Haemost 1993; 69: 1195 (abstr)
    PubMedGoogle Scholar
  • 45 Connolly TM, Condra C, Feng D-M, Cook JJ, Stranieri M, Reilly CF, Nutt RF, Gould RH. Species variability in platelet and other cellular responsiveness to thrombin receptor-derived peptides. Thromb Haemost 1994; 72: 627-633
    Article in Thieme ConnectPubMedGoogle Scholar
  • 46 Ferraris VA, Rodriquez E, Ferraris SP, Huang M, Gupta A, Bennett JA, Andersen TT, Dunn H, Fenton II JW, Smith JB. Platelet aggregation abnormalities after cardiopulmonary bypass. Blood 1994; 83: 299-300
    PubMedGoogle Scholar
  • 47 Rydel TJ, Ravishandraw KG, Tulinsky A, Bode W, Huber R, Roitsch C, Fenton II JW. The structure of a complex of recombinant hirudin and human a-thrombin. Science 1990; 249: 277-280
    CrossrefPubMedGoogle Scholar
  • 48 Fenton II JW, Ni F, Witting JI, Brezniak DV, Andersen TT, Malik AB. The rational design of thrombin-directed antithrombotics. Adv Exptl Biol Med 1992; 340: 1-14
    PubMedGoogle Scholar
  • 49 De Cristofaro R, Fenton II JW, Di Cera E. Modulation of thrombin- hirudin interaction by specific ion effects. J Mol Biol 1992; 226: 263-269
    CrossrefPubMedGoogle Scholar
  • 50 Konno S, Fenton II JW, Villanueva GB. Analysis of the secondary structure of hirudin and the conformational change upon interaction with thrombin. Arch Biochem Biophys 1988; 267: 158-166
    CrossrefPubMedGoogle Scholar
  • 51 Naski MC, Fenton II JW, Maraganore JM, Oson ST, Shafer JA. The C-terminal domain of hirudin on fibrinogen: and exosite directed competitive inhibitor of the action of a-thrombin on fibrinogen. J Biol Chem 1990; 265: 13484-13489
    PubMedGoogle Scholar
  • 52 Kane WH, Davie EW. Blood coagulation factors V and VIII: structural and functional similarities and their relationship to hemorrhagic and thrombotic disorders. Blood 1988; 71: 539-555
    PubMedGoogle Scholar
  • 53 Church FC, Pratt CW, Noyes CM, Kalayanamit T, Sherrill GB, Tobin RB, Meade JB. Structural and functional properties of human a-thrombin, phosphopyridoxylated a-thrombin, and Yt-thrombin. Identification of lysyl residues in a-thrombin that are critical for heparin and fibrin(ogen) interactions. J Biol Chem 1989; 264: 18419-18425
    PubMedGoogle Scholar
  • 54 Fenton II JW, Campbell WP, Harrington JC, Miller KD. Large scale preparation and preliminary characterization of human thrombin. Biochim Biophys Acta 1971; 229: 26-32
    CrossrefPubMedGoogle Scholar
  • 55 Sonder SA, Fenton II JW. Proflavin binding within the fibrinopep- tide groove adjacent to the catalytic site of human a-thrombin. Biochemistry 1984; 23: 1818-1823
    CrossrefPubMedGoogle Scholar
  • 56 Gaffney PJ, Heath AB, Fenton II JW. A collaborative study to establish an international standard for alpha-thrombin. Thromb Haemost 1992; 67: 424-427
    Article in Thieme ConnectPubMedGoogle Scholar
  • 57 Chen LB, Buchanan JM. Mitogenic activity of blood components. I. Thrombin and prothrombin. Proc Natl Acad Sci USA 1975; 72: 131-135
    CrossrefPubMedGoogle Scholar
  • 58 Markwardt F. Hirudin and derivatives as anticoagulant agents. Thromb Haemost 1991; 66: 141-152
    Article in Thieme ConnectPubMedGoogle Scholar
  • 59 Fenton II JW, Ni F, Witting JI, Brezniak DV, Anderson TT, Malik AB. The rational design of thrombin-directed antithrombotics. Adv Expt Med Biol 1993; 340: 1-13
    PubMedGoogle Scholar
  • 60 Maraganore JMaraganore. Thrombin, thrombin inhibitors, and the arterial thrombotic process. Thromb Haemost 1993; 70: 208-211
    Article in Thieme ConnectPubMedGoogle Scholar
  • 61 Dickels DDickels. Gene transfer in the treatment of thrombosis. Thromb Haemost 1993; 70: 198-201
    Article in Thieme ConnectPubMedGoogle Scholar
  • 62 Nabel EG, Nabel GJ. Direct gene transfer: basic studies and human therapies. Thromb Haemost 1993; 70: 202-203
    Article in Thieme ConnectPubMedGoogle Scholar
  • 63 Wittig JI, Brezniak DV, Hayes JR, Fenton II JW. Human α and ζ thrombin inhibition by recombinant HV1 and HV2K47 hirudins. Thromb Res 1991; 63: 473-479
    CrossrefPubMedGoogle Scholar