Advertisement

Plasminogen Activator Inhibitor-1

  • Daniel T. Eitzman
  • William P. Fay
  • David Ginsburg
Part of the Developments in Cardiovascular Medicine book series (DICM, volume 193)

Abstract

Fibrinolysis, the dissolution of fibrin clots, is an integral component of the hemostatic system that involves the concerted action of a complex system of zymogens, activators, and inhibitors [1]. Plasmin, the primary protease of the fibrinolysic system, digests fibrin, thereby converting insoluble clot to soluble fibrin degradation products. Plasmin formation is regulated, in large part, by plasminogen activators, which are responsible for converting the zymogen, plasminogen, to plasmin. The two major plasminogen activators in humans are tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). Both types of activators are serine proteases that specifically convert plasminogen to the broad-specificity protease, plasmin, by cleaving a single peptide bond (Arg560-Val561) [1]. Plasmin, in turn, appears to participate in a multitude of biological processes, including vascular fibrinolysis [2], ovulation [3], inflammation [4], tumor metastasis

Keywords

Plasminogen Activator Idiopathic Pulmonary Fibrosis Pulmonary Fibrosis Plasminogen Activator Inhibitor Hemolytic Uremic Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Francis CW, Marder VJ. Physiologic regulation and pathologic disorders of fibrinolysis. In Colman RW, Hirsh J, Marder VJ, Salzman EW (eds). Hemostasis and Thrombosis. Basic Principles and Clinical Practice, Peiladelphia: JB Lippincott, 1987:358.Google Scholar
  2. 2.
    Bachmann F. Fibrinolysis. In Verstraete M, Vermylen J, Lijnen HR, Arnout J (eds). Thrombosis and Haemostasis. Leuven, Belgium: Leuven University Press, 1987:227.Google Scholar
  3. 3.
    Hsueh AJW, Liu YX, Cajander SB, Ny T. Molecular mechanisms in the hormone regulation of plasminogen activator activity in ovarian granulosa cells and cumulus—oocyte complexes. In Haseltine FP, First NL (eds). Meiotic Inhibition: Molecular Control of Meiosis. New York: Liss, 1988:227.Google Scholar
  4. 4.
    Pöllänen J, Stephens RW, Vaheri A. Directed plasminogen activation at the surface of normal and malignant cells. Adv Cancer Res 57:273, 1991.PubMedGoogle Scholar
  5. 5.
    Dano K, Andreasen PA, Grondahl-Hansen J, Kristensen P, Nielsen LS, Skriver L. Plasminogen activators, tissue degradation, and cancer. Adv Cancer Res 44:139, 1985.PubMedGoogle Scholar
  6. 6.
    Moscatelli D, Riftcin DB. Membrane and matrix localization of proteinases: A common theme in tumor cell invasion and angiogenesis. Biochim Biophys Acta 948:67, 1988.PubMedGoogle Scholar
  7. 7.
    Saksela O, Rifkin DB. Cell-associated plasminogen activation: Regulation and physiological functions. Annu Rev Cell Biol 4:93, 1988.PubMedGoogle Scholar
  8. 8.
    Hoylaerts M, Rijken DC, Lijnen HR, Collen D. Kinetics of the activation of plasminogen by human tissue plasminogen activator. J Biol Chem 257:2912, 1982.PubMedGoogle Scholar
  9. 9.
    Ellis V, Dano K. Plasminogen activation by receptorbound urokinase. Semin Thromb Hemost 17:194, 1991.PubMedGoogle Scholar
  10. 10.
    Hajjar KA, Hamel NM. Identification and characterization of human endothelial cell membrane binding sites for tissue plaminogen activator and urokinase. J Biol Chem 265:2908, 1990.PubMedGoogle Scholar
  11. 11.
    Plow EF, Felez J, Miles LA. Cellular regulation of fibrinolysis. Thromb Haemost 66:32, 1991.PubMedGoogle Scholar
  12. 12.
    Kruithof EKO. Plasminogen activator inhibitors — a review. Enzyme 40:113, 1988.PubMedGoogle Scholar
  13. 13.
    Hart DA, Rehemtulla A. Plasminogen activators and their inhibitors: Regulators of extracellular proteolysis and cell function. Comp Biochem Physiol [B] 90B:691. 1988.Google Scholar
  14. 14.
    Aoki N. Hemostasis associated with abnormalities of fibrinolysis. Blood Rev 3:11, 1989.PubMedGoogle Scholar
  15. 15.
    Astedt B, Lecander I, Ny T. The placental type plasminogen activator PAI-2. Fibrinolysis 1:203, 1987.Google Scholar
  16. 16.
    Meijers JC, Chung DW. Organization of the gene coding for human protein C inhibitor (plasminogen activator inhibitor-3). Assignment of the gene to chromosome 14. J Biol Chem 266:15028, 1991.PubMedGoogle Scholar
  17. 17.
    Scott RW, Bergman BL, Bajpai A, Hersh RT, Rodriguez H, Jones BN, Barreda C, Watts S, Baker JB. Protease nexin. Properties and a modified purification procedure. J Biol Chem 260:7029, 1985.PubMedGoogle Scholar
  18. 18.
    van Mourik JA, Lawrence DA, Loskutoff DJ. Purification of an inhibitor plasminogen activator (antiactivator) synthesized by endothelial cells. J Biol Chem 259:14914, 1984.PubMedGoogle Scholar
  19. 19.
    Lawrence D, Strandberg L, Grundstrom T, Ny T. Purification of active human plasminogen activator inhibitor 1 from Escherichia coli. Comparison with natural and recombinant forms purified from eucaryotic cells. Eur J Biochem 186:523, 1989.PubMedGoogle Scholar
  20. 20.
    Boswell DR, Carrell RW. Genetic engineering and the SERPINs. Bioessays 8:83, 1988.PubMedGoogle Scholar
  21. 21.
    Huber R, Carrell RW. Implications of the three-dimensional structure of alpha 1-antitrypsin for structure and function of serpins. Biochemistry 28:8951, 1989.PubMedGoogle Scholar
  22. 22.
    Carrell R, Travis J. a1-Antitrypsin and the serpins: Variation and countervariation. Trends Biochem Sci 10:20, 1985.Google Scholar
  23. 23.
    Doolittle RF. Angiotensinogen is related to the antitrypsin-anrithrombin-ovalbumin family. Science 222:417. 1983.PubMedGoogle Scholar
  24. 24.
    Hunt LT, Dayhoff MO. A surprising new protein supertamily containing ovalbumin, antithrombin III, and alphal-protemase inhibitor. Biochem Biophys Res Commun 95:864, 1980.PubMedGoogle Scholar
  25. 25.
    Hekman CM, Loskutoff DJ. Bovine plasminogen activator inhibitor 1: Specificity determinations and comparison or the active, latent, and guanidine-activated forms. Biochemistry 27:2911, 1988.PubMedGoogle Scholar
  26. 26.
    Sakara Y, Curriden S, Lawrence D, Griffin JH, Loskutoff DJ. Activated protein C stimulates the fibnnolytic activity of cultured endothelial cells and decreases antiactivator activity. Proc Natl Acad Sci USA 82:1121, 1985.Google Scholar
  27. 27.
    Sakata Y, Loskutoff DJ, Gladson CL, Hekman CM, Griffin JH. Mechanism of protein C-dependent clot lysis: Role of plasminogen activator inhibitor. Blood 68:1218, 1986.PubMedGoogle Scholar
  28. 28.
    Hay WP, Owen WG. Platelet plasminogen activator inhibitor: Purification and characterization of interaction with plasminogen activators and activated protein C. Biochemistry 28:5773, 1989.Google Scholar
  29. 29.
    Ehrlich HJ, Gebbink RK, Keijer J, Linders M, Preissner KT, Pannekoek H. Alteration of serpin specificity by a protein cofactor. J Biol Chem 265:13029, 1990.PubMedGoogle Scholar
  30. 30.
    Declerck PJ, Verstreken M, Kruithof EKO, Juhan-Vague I, Collen D. Measurement of plasminogen activator inhibitor 1 in biologic fluids with a murine monoclonal antibody-based enzyme-linked immunoabsorbent assay. Blood 71:220, 1988.PubMedGoogle Scholar
  31. 31.
    Booth NA, Simpson AJ, Croll A, Bennett B, MacGregor IR. Plasminogen activator inhibitor (PA1-1) in plasma and platelets. Br J Haematol 70:327. 1988.PubMedGoogle Scholar
  32. 32.
    Colucci M, Páramo JA, Collen D. Generation in plasma of a fast-acting inhibitor of plasminogen activator in response to endotoxin stimulation. J Clin Invest 75:818, 1985.PubMedCrossRefGoogle Scholar
  33. 33.
    Vaughan DE, Declerck PJ, Van Houtte E, De Mol M, Collen D. Studies of recombinant plasminogen activator inhibitor-1 in rabbits. Pharmacokinetics and evidence for reactivation of latent plasminogen activator inhibitor-1 in vivo. Circ Res 67:1281, 1990.PubMedGoogle Scholar
  34. 34.
    Erickson LA. Ginsberg MH, Loskutoff DJ. Detection and partial characterization of an inhibitor of plasminogen activator in human platelets. J Clin Invest 74:1465, 1984.PubMedCrossRefGoogle Scholar
  35. 35.
    Sawdey MS, Loskutoff DJ. Regulation of murine type 1 plasminogen activator inhibitor gene expression in vivo. Tissue specificity and induction by lipopolysac-charide, tumor necrosis factor-a, and transforming growth factor-b. J Clin Invest 88:1346, 1991.PubMedCrossRefGoogle Scholar
  36. 36.
    Krishnamurti C, Alving BM. Plasminogen activator inhibitor type 1: Biochemistry and evidence for modulation of fibrinolysis in vivo. Semin Thromb Hemost 18:67, 1992.PubMedGoogle Scholar
  37. 37.
    Pyke C, Kristensen P, Ralfkiaer E, Eriksen J. Dano K. The plasminogen activation system in human colon cancer: Messenger RNA for the inhibitor PAI-1 is located in endothelial cells in the tumor stroma. Cancer Res 51:4067, 1991.PubMedGoogle Scholar
  38. 38.
    Schneiderman J, Sawdey MS, Kceton MR, Bordin GM, Bernstein EF, Dilley RB, Loskutoff DJ. Increased type 1 plasminogen activator inhibitor gene expression in atherosclerotic human arteries. Proc Natl Acad Sci USA 89:6998, 1992.PubMedGoogle Scholar
  39. 39.
    Keeton M, Eguchi Y, Sawdey M, Ahn C, Loskutoff DJ. Cellular localization of type 1 plasminogen activator inhibitor messenger RNA and protein in murine renal tissue. Am J Pathol 142:59, 1993.PubMedGoogle Scholar
  40. 40.
    Declerck PJ, De Mol M, Alessi MC, Baudner S, Pâques E-P, Preissner KT, Müller-Berghaus G, Collen D. Purification and characterization of a plasminogen activator inhibitor 1 binding protein from human plasma. J Biol Chem 263:15454, 1988.PubMedGoogle Scholar
  41. 41.
    Wiman B, Almquist A, Sigurdardottir O, Lindahl T. Plasminogen activator inhibitor 1 (PAI is bound to vitronectin in plasma. FEBS Lett 242:125, 1988.PubMedGoogle Scholar
  42. 42.
    Mimuro J, Schleef RR, Loskutoff DJ. Extracellular matrix of cultured bovine aortic endothehal cells contains functionally active type 1 plasminogen activator inhibitor. Blood 70:721, 1987.PubMedGoogle Scholar
  43. 43.
    Klinger KW, Winqvist R, Riccio A, Andreasen PA, Sartorio R, Nielsen LS, Stuart N, Stanislovitis P, Watkins P, Douglas R, Grzeschik K-H, Alitalo K, Blasi F, Dano K. Plasminogen activator inhibitor type 1 gene is located at region q21-3—q22 of chromosome 7 and genetically linked with cystic fibrosis. Proc Natl Acad Sci USA 84:8548, 1987.PubMedGoogle Scholar
  44. 44.
    Loskutoff DJ, Linders M, Keijer J, Veerman H, van Heerikhuizen H, Pannekoek H. Structure of the human plasminogen activator inhibitor 1 gene: Nonrandom distribution of introns. Biochemistry 26:3763, 1987.PubMedGoogle Scholar
  45. 45.
    Ginsburg D, Zeheb R, Yang AY, Rafferty UM, Andreasen PA, Nielsen L, Dano K, Lebo RV, Gelehrter TD. cDNA cloning of human plasminogen activator-inhibitor from endothelial cells. J Clin Invest 78:1673, 1986.PubMedGoogle Scholar
  46. 46.
    Loskutoff DJ, Sawdey M, Mimuro J. Type 1 plasminogen activator inhibitor. Prog Hemost Thromb 9:87, 1989.PubMedGoogle Scholar
  47. 47.
    Hekman CM, Loskutoff DJ. Endothelial cells produce a latent inhibitor of plasminogen activators that can be activated by denaturants. J Biol Chem 260:11581, 1985.PubMedGoogle Scholar
  48. 48.
    Stem P, Chothia C. Serpin tertiary structure transformation. Mol Biol 221:615, 1991.Google Scholar
  49. 49.
    Loebermann H, Tokuoka R, Deisenhofer J, Huber R. Human a1-proreinase inhibitor. Crystal structure analysis of two crystal modifications, molecular model and preliminary analysis of the implications for function. J Mol Biol 177:531, 1984.PubMedGoogle Scholar
  50. 50.
    Declerck PJ, De Mol M, Vaughan DE, Collen D. Identification of a conformationally distinct form of plasminogen activtor inhibitor-1, acting as a noninhibitory substrate for tissue-type plasminogen activator. J Biol Chem 267:11693, 1992.PubMedGoogle Scholar
  51. 51.
    Björk I, Ylinenjärvi K, Olson ST, Bock PE. Conversion of antithrombin from an inhibitor of thrombin to a substrate with reduced heparin affinity and enhanced conformational stability by binding of a tetradecapeptide corresponding to the P1, to P14 region of the putative reactive bond loop of the inhibitor. J Biol Chem 267:1976, 1992.PubMedGoogle Scholar
  52. 52.
    Schulze AJ, Baumann U, Knof S, Jaeger E, Huber R, Laurell C. Structural transition of a1,-antitrypsin by a peptide sequentially similar to b-strand s4A. Eur J Biochem 194:51, 1990.PubMedGoogle Scholar
  53. 53.
    Eitzman DT, Fay WP, Lawrence DA, Francis-Chmura AM, Shore JD, Olson ST, Ginsburg D. Peptide-mediated inactivation of recombinant and platelet plasminogen activator inhibitor-1 in vitro. J Clin Invest 95:2416, 1995.PubMedGoogle Scholar
  54. 54.
    Lawrence DA, Ginsburg D, Day DE, Berkenpas MB, Verhamme IM, Kvassman J-O, Shore JD. Serpinprotease complexes are trapped as stable acyl-enzyme intermediates. J Biol Chem 270:25309, 1995.PubMedGoogle Scholar
  55. 55.
    Sherman PM, Lawrence D, Paielli D, Olson S, Shore JD, Ginsburg D. Structure-function analysis of the plasminogen activator inhibitor-1 reactive center by site-directed mutagenesis (abstr). Fibrinolysis 4:267, 1990.Google Scholar
  56. 56.
    Berkenpas MB, Lawrence DA, Ginsburg D. Molecular evolution of plasminogen activator inhibitor-1 functional stability. EMBOJ 14:2969, 1995.Google Scholar
  57. 57.
    Levin EG, Santell L. Conversion of the active to latent plasminogen activator inhibitor from human endothelial cells. Blood 70:1090, 1987.PubMedGoogle Scholar
  58. 58.
    Seiffert D, Loskutoff DJ. Kinetic analysis of the interaction between type 1 plasminogen activator inhibitor and vitronectin and evidence that the bovine inhibitor binds to a thrombin-derived amino-terminal fragment of bovine vitronectin. Biochim Biophys Acta 1078:23, 1991.PubMedGoogle Scholar
  59. 59.
    Lawrence DA, Berkenpas MB, Palaniappan S, Ginsburg D. Localization of vitronectin binding domain in plasminogen activator inhibitor-1. J Biol Chem 269:15223, 1994.PubMedGoogle Scholar
  60. 60.
    Zheng X, Saunders TL, Camper SA, Samuelson LC, Ginsburg D. Vitronectin is not essential for normal mammalian development and fertility. Proc Natl Acad Sci USA 92:12426, 1995.PubMedGoogle Scholar
  61. 61.
    Naski MC, Lawrence DA, Mosher DF, Podor TJ, Ginsburg D. Kinetics of inactivation of a-thrombin by plasminogen activator inhibitor-1. J Biol Chem 268:12367, 1993.PubMedGoogle Scholar
  62. 62.
    Keijer J, Linders M, Wegman JJ, Ehrlich HJ, Mertens K, Pannekoek H. On the target specificity of plasminogen activator inhibitor 1: The role of heparin, vitronectin, and the reactive site. Blood 78:1254, 1991.PubMedGoogle Scholar
  63. 63.
    Edelberg JM, Reilly CF, Pizzo SV. The inhibition of tissue type plasminogen activator by plasminogen activator inhibitor-1. J Biol Chem 266:7488, 1991.PubMedGoogle Scholar
  64. 64.
    Keijer J, Linders M, van Zonneveld A-J, Ehrlich HJ, de Boer J-P, Pannekoek H. The interaction of plasminogen activator inhibitor 1 with plasminogen activators (tissue-type and urokinase-type) and fibrin: Localization of interaction sites and physiologic relevance. Blood 78:401, 1991.PubMedGoogle Scholar
  65. 65.
    Stringer HAR, Pannekoek H. The significance of fibrin binding by plasminogen activator inhibitor 1 for the mechanism of tissue-type plasminogen activator-mediated fibrinolysis. J Biol Chem 270:11205, 1995.PubMedGoogle Scholar
  66. 66.
    Fay WP, Eitzman DT, Shaprio AD, Madison EL, Ginsburg D. Platelets inhibit fibrinolysis in vitro by both plasminogen activator inhibitor-1 dependent and independent mechanisms. Blood 83:351, 1994.PubMedGoogle Scholar
  67. 67.
    Levi M, Biemond BJ, van Zonneveld A-J, Wourer Ten Care J, Pannekoek H. Inhibition of plasminogen activator inhibitor-1 activity results in promotion of endogenous thrombolysis and inhibirion of thrombus extension in models of experimental thrombosis. Circulation 85:305, 1992.PubMedGoogle Scholar
  68. 68.
    Lambers JW, Cammenga M, Konig BVC, Mertens K, Pannekoek H, van Mourik JA. Activation of human endothelial cell-type plasminogen activator inhibitor (PAI-1) by negatively charged phosphohpids. J Biol Chem 262:17492, 1987.PubMedGoogle Scholar
  69. 69.
    Wun T-C, Palmier MO, Siegel NR, Smith CE. Affinity purification of active plasminogen activator inhibitor-1 (PAI-1) using immobilized anhydrourokinase. J Biol Chem 264:7862, 1989.PubMedGoogle Scholar
  70. 70.
    Schleef RR, Higgins DL, Pillemer E, Levitt LJ. Bleeding diathesis due to decreased functional activity of Type 1 plasminogen activator inhibitor. J Clin Invest 83:1747, 1989.PubMedGoogle Scholar
  71. 71.
    Diéval J, Nguyen G, Gross S, Delobel J, Kruithof EKO. A lifelong bleeding disorder associated with a deficiency of plasminogen activator inhibitor type I. Blood 77:528, 1991.PubMedGoogle Scholar
  72. 72.
    Fay VCP, Shapiro AD, Shih JL, Schleef RR, Ginsburg D. Complete deficiency of plasminogen-activator inhibitor type 1 due to a frame-shift mutation. N Engl J Med 327:1729, 1992.PubMedCrossRefGoogle Scholar
  73. 73.
    Carmeliet P, Stassen JM, Schoonjans L, Ream B, van den Oord JJ, De Mol M, Mulligan RC, Collen D. Plasminogen activator inhibitor-1 gene-deficient mice. II. Effects on hemostasis, thrombosis, and thrombolysis. J Clin Invest 92:2756, 1993.PubMedGoogle Scholar
  74. 74.
    Carmeliet P, Schoonjans L, Kieckens L, Ream B, Degen JL, 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 368:419, 1994.PubMedGoogle Scholar
  75. 75.
    Ploplis VA, Carmeliet P, Vazirzadeh S, Van Vlaenderen I, Moons L, Plow EF, Colleen D. Effects of disruption of the plasminogen gene on thrombosis, growth, and health in mice. Circulation 92:2585, 1995.PubMedGoogle Scholar
  76. 76.
    Dawson SJ, Wiman B, Hamscen A, Geen F, Humphries S, Henney AM. The two allele sequences of a common polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-I) gene respond differently to interleukin-1 in HepG2 cells. J Biol Chem 268:10739, 1993.PubMedGoogle Scholar
  77. 77.
    Frikssnn P, Kallin B, Van’t Hooft FM, Båavenholm P, Hamsten A. Allele-specific increase in basal transcription of the plasminogen-activator inhibitor 1 gene is associated with myocardial infarction. Proc Natl Acad Sci USA 92:1851, 1995.Google Scholar
  78. 78.
    Ye S, Green FR, Scarabin PY, Nicaud V, Bara L, Dawson SJ, Humphries SF, Evans A, Luc G, Cambou JP, Arveiler D, Henney AM, Cambien F. The 4G/5G genetic polymorphism in the promoter of the plasmmogen activator inhibitor-1 (PAI-1) gene is associated with differences in plasma PAI-1 activity but not with risk of myocardial infarction in the ECTIM study. Thromb Haemost 74:837, 1995.PubMedGoogle Scholar
  79. 79.
    Vague-Julian I, Moerman B, DeCock F, Aillaud MF, Collen D. Plasma levels of a specific inhibitor of tissue-type plasminogen activator (and urokinase) in normal and pathological conditions. Thromb Res 33:523 1984.Google Scholar
  80. 80.
    Hamsten A, Wiman B, de Faire U. Blombäck M. Increased plasma levels of a rapid inhibitor of tissue plasminngen activator in young survivors of myocardial infarction. N Engl J Med 313:1557, 1985.PubMedCrossRefGoogle Scholar
  81. 81.
    Wiman B, Ljungberg B, Chmielewska J, Urden G, Blomhack M, Johnsson H. The role of the fibrinolytic system in deep vein thrombosis. J Lab Clin Med 105:265. 1985.PubMedGoogle Scholar
  82. 82.
    Paramo JA, Colucci M, Collen D, van de Werf F. Plasminogcn activator inhibitor in the blood of patients with coronary artery disease. Br Med J (Clin Res Ed) 291:573. 1985.Google Scholar
  83. 83.
    Aznar J, Estelles A, Tormo G, Sapena P, Tormo V, Blanch S, Espana F. Plasminogen activator inhibitor activity and other tibrinolytic variables in patients with coronary artery disese. Br Heart J 59:535, 1988.PubMedGoogle Scholar
  84. 84.
    Anglcs-Cano F, Gris JC, Loyau S, Schved JF. Familial association of high levels of histidine-rich glycoprotein and plasminogen activator inhibitor-1 with venous thromboembolism. J Lab Clin Med 121:646, 1993.Google Scholar
  85. 85.
    Ridker PM, Vaughan DF, Stampfer MJ, Manson JE, Shen C, Newcomer LM, Goldhaber SZ, Hennekens CH. Baseline fibrinolytic state and the risk of future venous thrombosis: A prospective study ol endogenous tissue-type plasminogen activator and plastninogen activator inhibitor. Circulation 85:1822, 1992.PubMedGoogle Scholar
  86. 86.
    Biemond BJ, Levi M, Coronel R, Janse MJ, ten Cate JW, Pannekoek H. Thrombolysis and reocclusion in experimental jugular vein and coronary artery thrombosis: Effects of a plasminogen activator inhibitor type 1-neutralizing monoclonal antibody. Circulation 91:1175, 1995.PubMedGoogle Scholar
  87. 87.
    Erickson LA, Fici GJ, Lund JF, Polites HG, Marotti KR. Transgenic mice expressing plasminogen activator inhibitor1 develop thrombotic vascular occlusions (abstr). Unknown 583a, 1989.Google Scholar
  88. 88.
    Lincoff AM, Topol EJ. Illusion of reperfusion. Does anyone achieve optimal reperfusion during acute myocardial infarction? Circulation 88:1361, 1993.PubMedGoogle Scholar
  89. 89.
    Kunitada S, Fitzgerald GA, Fitzgerald DJ. Inhibition of clot lysis and decreased binding of tissue-type plasminogen activator as a consequence of clot retraction. Blood 79:1420, 1992.PubMedGoogle Scholar
  90. 90.
    Robbie LA, Booth NA, Croll AM, Bennett B. The roles of a2-antiplasmm and plasnunogen activator inhibitor 1 (PAI-1) in the inhibition of clot lysis. Thromb Haemost 70:301, 1993.PubMedGoogle Scholar
  91. 91.
    McEver RP. Selectins: Novel receptors that mediate leukocyte adhesion during inflammation. Thromb Haemost 65:223, 1991.PubMedGoogle Scholar
  92. 92.
    Handt S, Jerome WG, Braaten JV, Lewis JC, Kirkpatrick CJ, Hantgan RR. PAI-1 released from cultured human endothelial cells delays fibrinolysis and is incorporated into the developing fibrin clot. Fibrinolysis 8:l04, 1994Google Scholar
  93. 93.
    Jang I-K, Gold HK, Ziskind AA, Fallon JT, Holt RF, Leinbach RC, May JW, Collen D. Differential sensitivity of eryrhrocyte-rich and platelet-rich arterial thrombi to lysis with recombinant tissuetype plasminogen activator. Circulation 79:920. 1989.PubMedGoogle Scholar
  94. 94.
    Stringer HAR, Van Swiften P, Heijnen HFG, Sixma JJ, Pannekoek H. Plasminogen activator inhibitor-1 released from activated platelets plays a key role in thrombolysis resistance. Studies with thrombi generated in the Chandler loop. Artenoscler Thromb 14:1452, 1994.Google Scholar
  95. 95.
    Hamsten A, de Faire U, Walldius G, Dahlen G, Szamosi A, Landou C, Blombäack M, Wiman B. Plasminogen activator inhibitor in plasma: Risk factor for recurrent myocardial infarction Lancet 23, 1987.Google Scholar
  96. 96.
    Adamson IY, bowden DH. The parhogenesjs of bleomycin-induced pulmonary fibrosis. Am J Pathol 77:185, 1974.PubMedGoogle Scholar
  97. 97.
    Perez RL, Roman J. Fibrin enhances the expression of IL-Ib by human peripheral blood mononuclear cells. Implications in pulmonary inflammation. J Immunol 154:1879, 1995.PubMedGoogle Scholar
  98. 98.
    Schwartz CJ, Valente AJ, Kelley JL, Sprague EA, Edwards EH. Thrombosis and the development of atherosclerosis: Rokitansky revisited. Semin Thromb Hemost 14:189, 1988.PubMedGoogle Scholar
  99. 99.
    Thompson WD, Smith EB. Atherosclerosis and the coagulation system. J Pathol 159:97. 1989.PubMedGoogle Scholar
  100. 100.
    Bacharach E, Itin A, Keshet E. In vivo patterns of expression of urokinasc and its inhibitor PAI-1 suggest a concerted role in regulating physiological angiogenesis. Proc Natl Acad Sci USA 89:10686, 1992.PubMedGoogle Scholar
  101. 101.
    Werb Z., Mainardi CL, Vater CA. Harris ED. Endogcnous activation of latent collagenase by synovial cells: Evidence for a role for plasm inogen activator. N Engl J Med 296:1017, 1977.PubMedCrossRefGoogle Scholar
  102. 102.
    Lawn RM, Wade DP, Hammer RE, Chiesa G, Verstuyft JG, Rubin EM. Atherogenesis in transgenic mice expressing human apolipoprotein (a). Nature 360:670, 1992.PubMedGoogle Scholar
  103. 103.
    Palabrica TM, Liu AC, Aronovitz MJ, Furie B, Lawn RM, Furie BC. Antifibrinolytic activity of apolipoprorein(a) in vivo: Human apolipoprotein(a) transgenic mice are resistant to tissue plasminogen activator-mediated thrombolysis. Nature Med 1:256, 1995.PubMedGoogle Scholar
  104. 104.
    Grainger DJ, Kirschenlohr HL, Metcalfe JC, Weissberg PL, Wade DP, Lawn RM. Proliferation of human smooth muscle cells promoted by lipoprotein(a). Science 260:1655, 1993.PubMedGoogle Scholar
  105. 105.
    Grainger DJ, Kemp PR, Liu AC, Lawn RM, Metcalfe JC. Activation of transforming growth factor-b is inhibited in transgenic apolipoprotien(a) mice. Narure 370:460, 1994.Google Scholar
  106. 106.
    Bertozzi P, Astedt B, Zenzius L, Lynch K, LeMaire F, Zapol W, Chapman HJ. Depressed bronchoalveolar urokinase activity in patients with adult respiratory distress syndrome. N Engl J Med 322:890, 1990.PubMedCrossRefGoogle Scholar
  107. 107.
    Fukuda Y, Ishizaki M, Masuda Y, Kimura G, Kawanami O, Masugi Y. 5768. Am J Pathol 126:171, 1987.PubMedGoogle Scholar
  108. 108.
    Idell S, James KK, Levin EG, Schwartz BS, Manchanda N, Maunder RJ, Martin TR, McLarty J, Fair DS. Local abnormalities in coagulation and fibrinolytic pathways predispose to alveolar fibrin deposition in the adult respiratory distress syndrome. J Clin Invest 84:695, 1989.PubMedGoogle Scholar
  109. 109.
    Chapman HA, Allen CL, Stone OL. Abnormalities in pathways of alveolar fibrin turnover among ptients with interstitial lung disease. Am Rev Respir Dis 133:437, 1986.PubMedGoogle Scholar
  110. 110.
    Hasday JL, Bachwich PR, Lynch JP, Sitrin RG. Procoagulanc and plasminogen accivacor activities of bronchoalveolar fluid in patients with pulmonary sarcoidosis. Exp Lung Res 14:261, 1988.PubMedGoogle Scholar
  111. 111.
    Viscardi RM, Broderick K, Sun CC, Yale LA, Hessamfar A, Taciak V, Burke KC, Koenig KB, Idell S. Disordered parhways of fibrin turnover in lung lavage of premature infants with respiratory distress syndrome. Am Rev Respir Dis 146:492, 1992.PubMedGoogle Scholar
  112. 112.
    Idell S, James KK, Gillies C, Fair DS, Thrall RS. Abnormalities of pathways of fibrin turnover in lung lavage of rats with oleic acid and bleomycin-induced lung injury support alveolar fibrin deposition. Am J Pathol 135:387, 1989.PubMedGoogle Scholar
  113. 113.
    Schrier DJ, Phan SH, McGarry BM. The effects of the nude (nu/nu) mutation of bleomycin-induced pulmonary fibrosis. A biochemical evaluation. Am Rev Respir Dis 127:614, 1983.PubMedGoogle Scholar
  114. 114.
    Idell S, Gonzales KK, MacArthur CK, Gillies C, Walsh PN, McLarty J, Thrall RS. Bronchoalveolar lavage procoagulanr activity in bleomycin-induced lung injury in marmosets. Characterization and relationship to fibrin deposition and fibrosis. Am Rev Respir Dis 136:124, 1987.PubMedGoogle Scholar
  115. 115.
    Wuelfroth P, Okada H, Vinogradsky B, Bell SP, Fujii S. A novel inhibitor of plasminogen activator inhibitor-1 in vitro modulates development of atherosclerosis in vivo in rabbits (abstr). Circulation 92:1–303, 1995.Google Scholar
  116. 116.
    Olman MA, Mackman N, Gladson CL, Moser KM, Loskutoff DJ. Changes in procoagulant and fibrinolytic gene expression during bleomycinlnduced lung injury in the mouse. J Clin Invest 96:1621, 1995.PubMedGoogle Scholar
  117. 117.
    Eitzman DT, McCoy RD, Zheng X, Fay WP, Shen T, Ginsburg D. Bleomycin-induced pulmonary fibrosis in transgenic mice that either lack or overexpress the murine plasminogen activator inhibitor-1 gene. J Clin Invest 97:232, 1996.PubMedGoogle Scholar
  118. 118.
    Bergstein JM, Riley M, Bang NU. Role of plasminogen-activator inhibitor type 1 in the pathogenesis and outcome of the hemolytic uremic syndrome. N Engl J Med 327:755, 1992.PubMedCrossRefGoogle Scholar
  119. 119.
    Keeton M, Ahn C, Eguchi Y, Burlingame R, Loskutoff DJ. Expression of type 1 plasminogen activator inhibitor in renal tissue in murine lupus nephritis. Kidney Int 47:148, 1995.PubMedGoogle Scholar
  120. 120.
    Cajot JF, Kruithof F.K, Schleuning WD, Sordat B, Bachmann F. Plasminogen activators, plasminogen activator inhibitors and procoagulant analyzed in twenty human tumor cell lines. Int J Cancer 38:719, 1986.PubMedGoogle Scholar
  121. 121.
    Hearing VJ, Law LW, Corti A, Appella E, Blasi F. Modulation of metastatic potential by cell surface urokinase of murine melanoma cells. Cancer Res 48:1270, 1988.PubMedGoogle Scholar
  122. 122.
    Pyke C, Kristensen P, Ralfkiaer E, Grondahl-Hansen J, Eriksen J, Blasi F, Dano K, Grndahl-Hansen J, Dan K. Urokinast-type plasminogen activator is expressed in scromal cells and its receptor in cancer cells at invasive foci in human colon adenocarcinomas. Am J Pathol 138:1059, 1991.PubMedGoogle Scholar
  123. 123.
    Mignatti P, Robbins E, Rifkin DB. Tumor invasion through the human amniotic membrane: Requirement for a proteinase cascade. Cell 47:487, 1986.PubMedGoogle Scholar
  124. 124.
    Ossowski L. In vivo invasion of modified chorioallantoic membrane by tumor cells: The role of cell surface-bound urokinase. J Cell Biol 107:2437, 1988.PubMedGoogle Scholar
  125. 125.
    Crowley CW, Cohen RL, Lucas BK, Liu G, Shuman MA, Levinson AD. Prevention of metastasis by inhibition of the urokinase receptor. Proc Natl Acad Sci USA 90:5021, 1993.PubMedGoogle Scholar
  126. 126.
    Sordat B, Reiter L, Cajot J-F. Modulation of the malignant phenotype with the urokinase-type plasminogen activator and the type 1 plasminogen activator inhibitor. Cell Different Dev 32:277, 1990.Google Scholar
  127. 127.
    Ossowski L, Reich E. Antibodies to plasminogen activaror inhibit human tumor metastasis. Cell 35:611, 1983.PubMedGoogle Scholar
  128. 128.
    Ossowski L. Plasminogen activator dependent pathways in the dissemination of human tumor cells in the chick embryo. Cell 52:321, 1988.PubMedGoogle Scholar
  129. 129.
    Eitzman DT, Krauss JC, Shen T, Cui J, Ginsburg D. Lack of plasminogen activator inhibitor-1 effect in a transgenic mouse model of metastatic melanoma. 1995, unpublished.Google Scholar
  130. 130.
    Lawrence DA, Ginsburg D. Plasminogen activator inhibitors. In High KA, Roberts HR (eds). Molecular Basis of Thrombosis and Hemostasis, New York: Marcel Dekker, 1995:517.Google Scholar
  131. 131.
    Stein PE, Carrell RW. What do dysfunctional serpins tell us about molecular mobility and disease? Struct Biol 2:96, 1995.Google Scholar

Copyright information

© Kluwer Academic Publishers 1997

Authors and Affiliations

  • Daniel T. Eitzman
  • William P. Fay
  • David Ginsburg

There are no affiliations available

Personalised recommendations