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The Biochemistry of Thrombolytic Agents

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Acute Coronary Care

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Abstract

The use of thrombolytic agents for the treatment of acute myocardial infarction has recently received new impetus. There are two major reasons for this. First is the development and perfection of coronary angiography, which allows direct visualization of the acutely thrombosed coronary artery and subsequent administration of thrombolytic agents in proximity to the clot [1, 2]. Second, a highly purified streptokinase preparation is now available that is less allergenic than earlier preparations. This chapter reviews the biochemical and physiological properties of the therapeutic agents that promote thrombolysis by “activation,” or conversion of plasminogen into plasmin. There are two available thrombolytic agents, urokinase and streptokinase, and another tissue plasminogen activator that has recently been isolated, purified, characterized, and resynthesized through recombinant DNA technology.

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References

  1. Rentrop P, Blanke H, Karsch KR, Kaiser H, Kostering H, Leitz K: Selective intracoronary thrombolysis in acute myocardial infarction and unstable angina pectoris. Circulation 63: 307–317, 1981.

    Article  PubMed  CAS  Google Scholar 

  2. Ganz W: Intracoronary thrombolysis in evolving acute myocardial infarction. Am Heart J XX: 101–104, 1981.

    Google Scholar 

  3. Barlow GH: Urinary and kidney cell plasminogen activator (urokinase). Methods Enzymol 45: 239–244, 1976.

    Article  PubMed  CAS  Google Scholar 

  4. Markus G, Takita H, Camiolo SM, Corasanti JG, Evers JL, Hobika GH: Content and characterization of plasminogen activators in human lung tumors and normal lung tissue. Cancer Res 40: 841–848, 1980.

    PubMed  CAS  Google Scholar 

  5. Summaria L, Hsieh B, Robbins KC: The specific mechanism of activation of human plasminogen toplasmm. J Biol Chem 242: 4279–4287, 1967.

    PubMed  CAS  Google Scholar 

  6. McClintock DK, Bell PH: Mechanism of activation of human plasminogen by streptokinase. Biochem Biophys Res Commun 43: 694–702, 1971.

    Article  PubMed  CAS  Google Scholar 

  7. Jackson KW, Tang J: Complete amino acid sequence of streptokinase and its homology with serine proteases. Biochemistry 21: 6620–6625, 1982.

    Article  PubMed  CAS  Google Scholar 

  8. Sottrup-Jensen L, Claeys H, Sajdel M, Petersen RE, Magnussen S: The primary structure of human plasminogen. Prog Chem Fibrinolysis 3: 191–199.

    Google Scholar 

  9. Reddy KNN, Markus G: Mechanism of activation of human plasminogen by streptokinase: presence of an active center in streptokinase—plasminogen complex. J Biol Chem 247: 1683–1691, 1972.

    PubMed  CAS  Google Scholar 

  10. Markus G, Evers JL, Hobika GH: Activator ac-tivities of the transient forms of the human plasminogen—streptokinase complex during its pro-teolytic conversion to the stable activator complex. J Biol Chem 251: 6495–6504, 1976.

    PubMed  CAS  Google Scholar 

  11. Gonzalez-Gronow M, Siefring CE, Castellino FJ: The mechanism of activation of human plasminogen by the activator complex streptokinase— plasmin. J Biol Chem 253: 1090–1094, 1978.

    PubMed  CAS  Google Scholar 

  12. Summaria L, Arzadon L, Bernabe P, Robbins KC: The interaction of streptokinase with human, cat, dog and rabbit plasminogens: the fragmentation of streptokinase in the equimolar plasminogen—streptokinase complexes. J Biol Chem 249: 4760–4769, 1974.

    PubMed  CAS  Google Scholar 

  13. Summaria L, Robbins KC: Barlow GH: Dissocia-tion of the equimolar human plasmin—strepto-kinase complex: partial characterization of the isolated plasmin and streptokinase moieties. J Biol Chem 246: 2136–2142, 1971.

    CAS  Google Scholar 

  14. Summaria L, Arzadon R, Bernabe P, Robbins KC: Characterization of the NH2-terminal glutamic acid and NH2-terminal lysine forms of human plasminogen isolated by affinity chromatography and isoelectric focusing methods. J Biol Chem 248: 2984–2991, 1973.

    PubMed  CAS  Google Scholar 

  15. Summaria L, and Robbins KC: Isolation of a human plasmin-derived, functionally active, light (B) chain, capable of forming with streptokinase an equimolar light (B) chain—streptokinase complex with plasminogen activator activity. J Biol Chem 251: 5810–5813, 1976.

    PubMed  CAS  Google Scholar 

  16. Wohl RC, Summaria L, Arzadon L, Robbins KC: Steady state kinetics of activation of human and bovine plasminogens by streptokinase and its equimolar complexes with various activated forms of human plasminogen. J Biol Chem 253: 1402–1407, 1978.

    PubMed  CAS  Google Scholar 

  17. Summaria L, Boreisha I, Barlow GH, Robbins KC: The isolation and characterization of an equimolar human light (B) chain—streptokinase plasminogen complex. Circulation (Suppl 2 ) 66: 11–179, 1982.

    Google Scholar 

  18. Kakkar VV: Intermittent plasminogen—streptokinase treatment of deep-vein thrombosis. Prog Fibrinolysis 5: 420–431.

    Google Scholar 

  19. Cole ER, Bachmann FW: Purification and properties of plasminogen activator from pig heart. J Biol Chem 252: 3729–3737, 1977.

    PubMed  CAS  Google Scholar 

  20. Kok P, Astrup T: Isolation and purification of a tissue plasminogen activator and its comparison with urokinase. Biochemistry 8: 79–86, 1969.

    Article  PubMed  CAS  Google Scholar 

  21. Unkelless J, Dano K, Kellerman GM, Reich E: Fibrinolysis associated with oncogenic transformation: partial purification and characterization of the cell factor, a plasminogen activator. J Biol Chem 249: 4295–4305, 1974.

    Google Scholar 

  22. Rifkin DB, Loeb JN, Moore G, Reich E: Properties of plasminogen activators formed by neoplastic human cell cultures. J Exp Med 139: 1317–1325, 1974.

    Article  PubMed  CAS  Google Scholar 

  23. Christman JK, Acs G, Silagi S, Silverstein SC: Plasminogen activator: biochemical characterization and correlation with tumorigenicity. Proteases Biol Control XX: 827–839, 1975.

    Google Scholar 

  24. Aasted B: Immunochemical characterization of human plasminogen activators. Biochim Biophy Acta 668: 339–348, 1981.

    CAS  Google Scholar 

  25. Binder BR, Spragg J, Austen KF: Purification and characterization of human vascular plasminogen activator derived from blood vessel perfusates. J Biol Chem 254: 1998–2003, 1979.

    PubMed  CAS  Google Scholar 

  26. Allen RA, Pepper DS: Isolation and properties of human vascular plasminogen activator. Thromb Haemost 45: 43–50, 1981.

    PubMed  CAS  Google Scholar 

  27. Collen D: On the regulation and control of fibri-nolysis. Thromb Haemost 43: 77–89, 1980.

    PubMed  CAS  Google Scholar 

  28. Collen D, Rijken DC, Van Damme J, Billiau A: Purification of human tissue-type plasminogen activator in centigram quantities from human melanoma cell culture fluid and its conditioning for use in vivo. Thromb Haemost 48: 294–296, 1982.

    PubMed  CAS  Google Scholar 

  29. Pennica D, Holmes WE, Kohr WJ, Harkins RN, Vehar GA, Ward CA, Bennett WF, Yelverton E, Seeburg PH, Heyneker HL, Goeddel DV, Collen D: Cloning and expression of human tissue-type plasminogen activator CDNA in E. colt. Nature 301: 214–221, 1983.

    Article  CAS  Google Scholar 

  30. Bergmann SR, Fox KAA, Ter-Pogossian MM, Sobel BE, Collen D: Clot selective coronary thrombolysis with tissue type plasminogen activator. Science 220: 1181–1183, 1983.

    Article  PubMed  CAS  Google Scholar 

  31. Wohl RC, Sinio L, Robbins KC: Methods for studying fibrinolytic pathway components in human plasma. Thromb Res 27: 523–535, 1982.

    Article  PubMed  CAS  Google Scholar 

  32. Wohl, RC, Summaria L, ChediakJ, Rosenfeld S, Robbins KC: Human plasminogen variant, Chicago III. Thromb Haemost 48: 146–152, 1982.

    PubMed  CAS  Google Scholar 

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Authors
  1. Louis Summaria
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Editors and Affiliations

  1. Department of Medicine, Duke University Medical Center, Box 31123, 27710, Durham, North Carolina, USA

    Robert M. Califf M.D.

  2. Department of Medicine, Duke University Medical Center, Box 31211, 27710, Durham, North Carolina, USA

    Galen S. Wagner M.D.

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© 1985 Martinus Nijhoff Publishing, Boston/Dordrecht/Lancaster

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Summaria, L. (1985). The Biochemistry of Thrombolytic Agents. In: Califf, R.M., Wagner, G.S. (eds) Acute Coronary Care. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-3828-4_7

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  • DOI: https://doi.org/10.1007/978-1-4613-3828-4_7

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-3830-7

  • Online ISBN: 978-1-4613-3828-4

  • eBook Packages: Springer Book Archive

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