Role of Endothelial Plasminogen Activators in Fibrinolysis and Repair-Associated Angiogenesis

Two Sides of a Coin
  • Victor W. M. van Hinsbergh
  • Pieter Koolwijk
  • Erik Ponfoort
  • Roeland Hanemaaijer
  • Jef. J. Emeis
  • Teake Kooistra
  • Paul H. A. Quax
Part of the NATO ASI Series book series (NSSA, volume 294)

Abstract

Fibrin is a temporary matrix, which is formed after wounding a blood vessel and when plasma leaks from blood vessels forming a fibrous exudate, often seen in areas of inflammation and in tumors (Dvorak et al., 1992). The fibrin matrix not only acts as a barrier preventing further blood loss, but also provides a structure in which new microvessels can infiltrate during wound healing. Proper timing of the outgrowth of microvessels as well as the subsequent (partial) disappearance of these vessels is essential to ensure adequate wound healing and to prevent the formation of scar tissue. It is generally believed that plasminogen activators play an important role in the migration and invasion of leukocytes and endothelial cells, and in the dissolution of the fibrin matrix (Kwaan, 1966; Pepper et al., 1990; Koolwijk et al., 1996). Plasminogen activators are serine proteases, which enzymatically convert the zymogen plasminogen into the active protease plasmin, the prime protease that degrades fibrin. The production of plasminogen activators by endothelial cells not only contributes to the proteolytic events related to the formation of microvessels in a wound, but also plays a crucial role in the prevention of thrombosis. If fibrin becomes deposited within the lumen of a blood vessel, cessation of the blood flow may occur accompanied by ischemia and eventually death of the distal tissues. The endothelium contributes considerably to the maintenance of blood fluidity by exposing anticoagulant molecules, by providing factors that interfere with platelet aggregation, and by its ability to stimulate fibrinolysis. Lysis of intravascularly generated fibrin must occur rapidly. However, it should be limited to a local area, because a general elevation of fibrinolysis upon wounding would result in recurrent bleeding.

Keywords

Endothelial Cell Vascular Endothelial Growth Factor Plasminogen Activator Human Umbilical Vein Endothelial Cell Basic Fibroblast Growth Factor 
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.

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References

  1. Aiello, L.P., Avery, R.L., Arrigg, P.G., Keyt, B.A., Jampel, H.D., Shah, S.T., Pasquale, L.R. et al. Vascular endothelial cell growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders. N. Engl. J. Med., 331:1480–1487, 1994.PubMedCrossRefGoogle Scholar
  2. Appella, E., Robinson, E. A., Ullrich, S. J., Stoppelli, M. P., Corti, A., Cassani, G., and Blasi, F. The receptor-binding sequence of urokinase A biological function for the growth-factor module of proteases. J. Biol. Chem., 262:4437–4440, 1987.PubMedGoogle Scholar
  3. Ausprunk, D. and Folkman, J. Migration and proliferation of endothelial cells in preformed and newly formed blood vessels during tumor angiogenesis. Microvasc. Res., 14:52–65, 1977.CrossRefGoogle Scholar
  4. Bachmann, F. Fibrinolysis, in: Thrombosis and Haemostasis 1987, M. Verstraete, J. Vermylen, R. Lijnen, and J. Arnout, eds., pp. 227–265, Leuven University Press, Leuven, 1987.Google Scholar
  5. Bachmann, F. The enigma PAI-2. Gene expression, evolutionary and functional aspects. Thromb. Haemostas., 74:172–179,1995.Google Scholar
  6. Barnathan, E.S., Kuo, A., Van der Keyl, H., McCrae, K.R., Larsen, G.R. and Cines, D.B. Tissue-type plasminogen activator binding to human endothelial cells. Evidence for two distinct sites. J. Biol. Chem., 263:7792–7799, 1988.PubMedGoogle Scholar
  7. Barnathan, E. S. Characterization and regulation of the urokinase receptor of human endothelial cells. Fibrinolysis, 6:1–9, 1992.Google Scholar
  8. Beebe, D. P. Binding of tissue plasminogen activators to human umbilical vein endothelial cells. Thromb. Res., 46:241–254, 1987.PubMedCrossRefGoogle Scholar
  9. Blasi, F. Urokinase and urokinase receptor — A paracrine/autocrine system regulating cell migration and invasiveness. Bioessays, 15:105–111,1993.PubMedCrossRefGoogle Scholar
  10. Blasi, F., Conese, M., Møller, L. B., Pedersen, N., Cavallaro, U., Cubellis, M., Fazioli, F., Hernandez-Marrero, L., Limongi, P., Munoz-Canoves, P., Resnati, M., Riittinen, L., Sidenius, N., Soravia, E., Soria, M., Stoppelli, M., Talarico, D., Teesalu, T., and Valcamonica, S. The urokinase receptor: Structure, regulation and inhibitor-mediated internalization. Fibrinolysis, 8:182–188, 1994.Google Scholar
  11. Bonfanti, R., Furie, B. C., Furie, B., and Wagner, D. D. PADGEM (GMP140) is a component of Weibel-Palade bodies of human endothelial cells. Blood, 73:1109–1112, 1989.PubMedGoogle Scholar
  12. Broadley, K.N., Aquino, A.M., Woodward, S.C., Buckley-Sturrock, A., Sato, Y., Rifkin, D. and Davidson, J.M. Monospecific antibodies implicate basic fibroblast growth factor in normal wound repair. Lab. Invest. 61: 571–575, 1989.PubMedGoogle Scholar
  13. Brooks, P.C., Clark, R.A. and Cheresh, D.A. Requirement of vascular integrin αvβ3 for angiogenesis. Science 264:569–571, 1994a.PubMedCrossRefGoogle Scholar
  14. Brooks, P.C., Montgomery, A.M., Rosenfeld, M., Reisfeld, R.A., Hu, T., Klier, G and Cheresh, D.A. Intergrin αvβ3 antagonists promote tumor regression by inducing apoptosis of angiogenic blood vessels. Cell, 79:1157–1164, 1994b.PubMedCrossRefGoogle Scholar
  15. Brooks, P.C., Strömblad, S., Sanders, L.C., von Schalscha, T.L., Aimes, R.T., Stetler-Stevenson, W.G., Quigley, J.P., and Cheresh, D.A. Localization of matrix metalloproteinase MMP-2 to the surface of invasive cells by interaction with integrin αvβ3. Cell, 85:683–693, 1996.PubMedCrossRefGoogle Scholar
  16. Bu, G., Warshawsky, I., and Schwartz, A. L. Cellular receptors for the plasminogen activators. Blood, 83:3427–3436, 1994.PubMedGoogle Scholar
  17. Bu, G., Williams, S., Strickland, D.K. and Schwartz, A.L. Low density lipoprotein receptor-related protein/α2-macroglobulin receptor is an hepatic receptor for tissue-type plasminogen activator. Proc. Natl. Acad. Sci. U.S.A., 89:7427–7431, 1992.PubMedCrossRefGoogle Scholar
  18. Bugge, T.H., Suh, T.T., Flick, M.J., Daugherty, C.C., Rømer, J., Solberg, H., Ellis, V., Danø, K. and Degen, J.J. The receptor for urokinase-type plasminogen activator is not essential for mouse development or fertility. J. Biol. Chem. 270:16886–16894, 1995a.PubMedCrossRefGoogle Scholar
  19. Bugge, T.H., Flick, M.J., Daugherty, C.C., and Degen, J.L. Plasminogen deficiency causes severe thrombosis but is compatible with development and reproduction. Genes & Development, 9:794–807, 1995b.CrossRefGoogle Scholar
  20. Bunce, L. A., Sporn, L.A. and Francis, C.W. Endothelial cell spreading on fibrin requires flbrinopeptide B cleavage and amino acid residues 15–42 of the β-chain. J. Clin. Invest., 89:842–850, 1992.PubMedCrossRefGoogle Scholar
  21. Burgess, W.H., and Maciag, T. The heparin-binding (fibroblast) growth factor family of proteins. Annu. Rev. Biochem., 58:575–606, 1989.PubMedCrossRefGoogle Scholar
  22. Carmeliet, P., Schoonjans, L., Kieckens, L., Ream, B., Degen, J., Bronson, R., De Vos, R., Van den Oord, J. J., Collen, D., and Mulligan, R. C. Physiological consequences of loss of plasminogen activator gene function in mice. Nature, 368:419–424, 1994.PubMedCrossRefGoogle Scholar
  23. Carmeliet, P. and Collen, D. Evaluation of the plasminogen/plasmin system in transgenic mice. Fibrinolysis 8:269–276, 1994.Google Scholar
  24. Carmeliet, P., Stassen, J. M., Schoonjans, L., Ream, B., Van den Oord, J. J., De Mol, M., Mulligan, R. C., and Collen, D. Plasminogen activator inhibitor-1 gene-deficient mice. II. Effects on hemostasis, thrombosis, and thrombolysis. J. Clin. Invest., 92:2756–2760, 1993.PubMedCrossRefGoogle Scholar
  25. Carmeliet, P., Kieckens, L., Schoonjans, L., Ream, B., Van Nuffelen, A., Prendergast, G., Cole, M., Bronson, R., Collen, D., and Mulligan, R. C. Plasminogen activator inhibitor-1 gene-deficient mice. I. Generation by homologues recombination and characterization. J. Clin. Invest., 92:2746–2755, 1994.CrossRefGoogle Scholar
  26. Chang M-C., Wang, B-R. and Huang T-F. Characterization of endothelial cell differential attachment to fibrin and fibrinogen and its inhibition by Arg-Gly-Asp-containing peptides. Thromb. Haemostas., 74:764–769, 1995.Google Scholar
  27. Ciambrone, G. J., and McKeown-Longo, P. J. Vitronectin regulates the synthesis and localization of urokinase-type plasminogen activator in HT-1080 cells. J. Biol. Chem., 267:13617–13622, 1992.PubMedGoogle Scholar
  28. Clowes, A.W., Clowes, M.M., Au, Y.P.T., Reidy, M.A. and Belin, D. Smooth muscle cells express urokinase during mitogenesis and tissue-type plasminogen activator during migration in injured rat carotid artery. Circ. Res. 67:61–67, 1990.PubMedCrossRefGoogle Scholar
  29. Colucci, M., Paramo, J.A., and Collen, D., Generation in plasma of a fast-acting inhibitor of plasminogen activator in response to endotoxin stimulation. J. Clin. Invest., 75:818–824, 1985.PubMedCrossRefGoogle Scholar
  30. Colvin R.B. Wound Healing Processes in Hemostasis and Thrombosis, in: “Vascular Endothelium in Hemostasis and Thrombosis,” M.A. Gimbrone Jr., ed., pp. 220–241, Churchill Livingstone, Edinburgh, 1986.Google Scholar
  31. Conforti, G., Dominguez-Jimenez, C., Rønne, E., Høyer-Hansen, G., and Dejana, E. Cell-surface plasminogen activation causes a retraction of in vitro cultured human umbilical vein endothelial cell monolayer. Blood, 83:994–1005, 1994.PubMedGoogle Scholar
  32. Cornelius, L. A., Nehring, L. C., Roby, J. D., Parks, W. C., and Welgus, H. G. Human dermal microvascular endothelial cells produce matrix metalloproteinases in response to angiogenic factors and migration. J. Invest. Dermatol., 105:170–176, 1995.PubMedCrossRefGoogle Scholar
  33. Danø, K., Andreasen, P.A., Grøndahl-Hansen, J., Kristensen, P., Nielsen, L.S. and Skriver, L. Plasminogen activators in tissue degradation and cancer. Adv. Cancer Res. 44:139–264, 1985.PubMedCrossRefGoogle Scholar
  34. Danø, K., Behrendt, N., Brünner, N., Ellis, V., Ploug, M., and Pyke, C. The urokinase receptor Protein structure and role in plasminogen activation and cancer invasion. Fibrinolysis, 8:189–203, 1994.Google Scholar
  35. Davies, P.F., Robotewsky, A., Griem, M.L., Quantitative studies of endothelial adhesions: directional modeling of focal adhesion sites in response to flow forces. J. Clin. Invest. 93:2031–2038, 1994.PubMedCrossRefGoogle Scholar
  36. Dejana E., Lampugnani, M.G., Giorgi, M., Gaboli, M., and Marchisio, P.C. Fibrinogen induces endothelial cell adhesion and spreading via the release of endogenous matrix proteins and the recruitment of more than one integrin receptor. Blood, 75:1509–1517, 1990.PubMedGoogle Scholar
  37. Diamond, S.L., Eskin, S.G., and McIntire, L.V. Fluid flow stimulates tissue plasminogen activator secretion by cultured human endothelial cells. Science, 243:1483–1485,1989.PubMedCrossRefGoogle Scholar
  38. Dumler, I., Petri, T., and Schleuning, W-D. Interaction of urokinase-type plasminogen activator (u-PA) with its cellular receptor (u-PAR) induces phosphorylation on tyrosine of a 38 kDa protein. FEBS Letters, 322:37–40, 1993.PubMedCrossRefGoogle Scholar
  39. Dvorak, H.F. Tumors: wounds that do not heal: similarities between tumor stroma generation and wound healing. N. Engl. J. Med. 315:1650–1659, 1986.PubMedCrossRefGoogle Scholar
  40. Dvorak, H. F., Nagy, J. A., Berse, B., Brown, L. F., Yeo, K-T., Yeo, T-K., Dvorak, A. M, Van De Water, L., Sioussat, T. M, and Senger, D. R. Vascular permeability factor, fibrin, and the pathogenesis of tumor stroma formation. Ann. N. Y. Acad. Sci., 667:101–111, 1992.PubMedCrossRefGoogle Scholar
  41. Dvorak, H. F., Brown, L. F., Detmar, M., and Dvorak, A. M. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis. Am. J. Pathol., 146:1029–1039, 1995.PubMedGoogle Scholar
  42. Emeis, J. J. Regulation of the acute release of tissue-type plasminogen activator from the endothelium by coagulation activation products. Ann. N. Y. Acad. Sci., 667:249–258, 1992.PubMedCrossRefGoogle Scholar
  43. Emeis, J.J., and Kooistra, T. Interleukin-1 and lipopolysaccharide induce a fast-acting inhibitor od tissue-type plasminogen activator in vivo and in cultured endothelial cells. J. Exp. Med. 163:1260–1266, 1986.PubMedCrossRefGoogle Scholar
  44. Emeis, J.J., and Kooistra, T. Animal models and experimental procedures to study the synthesis and acute release of tissue-type plasminogen activator, Fibrinolysis 7, Suppl. 1:31–32, 1993.Google Scholar
  45. Emeis, J.J., van den Eijnden-Schrauwen, Y., and Kooistra, T. Tissue-type plasminogen activator and the vessel wall: synthesis, storage and secretion, in: “Vascular Control of Hemostasis”, V.W.M. van Hinsbergh ed., pp. 187–206, Harwood Acad. Publ., Amsterdam, 1996.Google Scholar
  46. Erban J.K. and Wagner D.D. A 130-kDa protein on endothelial cells binds to amino acids 15–42 of the Bβ chain of fibrinogen. J. Biol. Chem. 267:2451–2458, 1992.PubMedGoogle Scholar
  47. Estreicher, A., Mühlhauser, J., Carpentier, J-L., Orci, L., and Vassalli, J-D. The receptor for urokinase type plasminogen polarizes expression of the protease to the leading edge of migrating monocytes and promotes degradation of enzyme inhibitor complexes. J. Cell Biol., 111:783–792, 1990.PubMedCrossRefGoogle Scholar
  48. Fearns, C., Samad, F., and Loskutoff, D.J. Synthesis and localization of PAI-1 in the vessel wall, in: “Vascular Control of Hemostasis”, V.W.M. van Hinsbergh ed., pp. 207–226, Harwood Acad. Publ., Amsterdam, 1996.Google Scholar
  49. Feng, P., Ohlsson, M., and Ny, T. The structure of the TATA-less rat tissue-type plasminogen activator gene. Species-specific sequence divergences in the promoter predict differences in regulation of gene expression, J. Biol. Chem., 265:2022–2027, 1990.PubMedGoogle Scholar
  50. Fisher, C., Gilbertsonbeadling, S., Powers, E.A., Petzold, G., Poorman, R., and Mitchell, M.A. Interstitial collagenase is required for angiogenesis in vitro. Dev. Biol. 162:499–510, 1994.PubMedCrossRefGoogle Scholar
  51. Foda, H.D., George, S., Conner, C., Drews, M., Tomkins, D.C., Zucker, S. Activation of human umbilical vein endothelial cell progelatinase A by phorbol myristate: a protein kinase C-dependent mechanism involving a membrane-type matrix metalloproteinase. Lab. Invest. 74:538–545, 1996.PubMedGoogle Scholar
  52. Folkman, J. Tumor angiogenesis. in: “The Molecular Basis of Cancer”, J. Mendelsohn, P.M. Howley, M.A. Israel, and L.A. Liotta, eds., pp. 206–232, W.B. Saunders Comp., Philadelphia, 1995.Google Scholar
  53. Fong, G-H., Rossant, J., Gertsenstein, M. and Breitman, M.L. Role of the flt-1 receptor tyrosine kinase in regulating the assembly of vascular endothelium. Nature, 376:66–70, 1995.PubMedCrossRefGoogle Scholar
  54. Franke, R.P., Gräfe, M., Schnittler, H., Seiffge, D., Mittermayer, C., and Drenckhahn, D. Induction of human vascular endothelial stress fibres by fluid shear stress. Nature, 307:648–649, 1984.PubMedCrossRefGoogle Scholar
  55. Fràter-Schröder, M., Risau, W., Hallman, R., Gautschi, P., and Böhlen, P. Tumor necrosis factor type α, a potent inhibitor of endothelial cell growth in vitro, is angiogenic in vivo. Proc. Natl. Acad. Sci. USA, 84:5277–5281, 1987.PubMedCrossRefGoogle Scholar
  56. Friedlander, M., Brooks, P.C., Shaffer, R.W., Kincais, C.M., Varner, J.A. and Cheresh, D.A. Definition of two angiogenic pathways by distinct αv integrins. Science, 270:1500–1502, 1995.PubMedCrossRefGoogle Scholar
  57. Galis Z.S., Sukhova, G.K., Lark, M.W., and Libby, P. Increased expression of matrix metalloproteinases and matrix degrading activity in vulnerable regions of human atherosclerotic plaques. J. Clin. Invest., 94:2493–2503, 1994.PubMedCrossRefGoogle Scholar
  58. Grondahl-Hansen, J., Kirkeby, L., Ralfkiær, Kristensen, P., Lund, L.R., Danø, K. Urokinase-type plasminogen activator in endothelial cells during acute inflammtion of the appendix. Am. J. Pathol. 135:631–636, 1989.PubMedGoogle Scholar
  59. Gualandris, A., and Presta, M. Transcriptional and posttranscriptional regulation of urokinase-type plasminogen activator expression in endothelial cells by basic fibroblast growth factor. J. Cell. Physiol., 162:400–409, 1995.PubMedCrossRefGoogle Scholar
  60. Haddock, R. C., Spell, M. L., Baker III, C. D., Grammer, J. R, Parks, J. M., Speidel, M., and Booyse, F. M. Urokinase binding and receptor identification in cultured endothelial cells. J. Biol. Chem., 266:21466–21473, 1991.PubMedGoogle Scholar
  61. Hajjar, K.A. The endothelial cell tissue plasminogen activator receptor. Specific interaction with plasminogen. J. Biol. Chem. 266:21962–21970, 1991.PubMedGoogle Scholar
  62. Hajjar, K. A. Cellular receptors in the regulation of plasmin generation. Thromb. Haemostas., 74:294–301, 1995.Google Scholar
  63. Hajjar, K.A., and Nachman, 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. 82:1769–1778, 1988.PubMedCrossRefGoogle Scholar
  64. Hajjar, K. A., and Reynolds, C. α-Fucose-mediated binding and degradation of tissue-type plasminogen activator by HepG2 cells. J. Clin. Invest., 93:703–710, 1994.PubMedCrossRefGoogle Scholar
  65. Hajjar, K. A., Hamel, N. M., Harpel, P. C., and Nachman, R. L. Binding of tissue plasminogen activator to cultured human endothelial cells. J. Clin. Invest., 80:1712–1719, 1987.PubMedCrossRefGoogle Scholar
  66. Hajjar, K., Jacovina, A. and Chacko, J. An endothelial cell receptor for plasminogen tissue plasminogen activator 1 identity with annexin II. J. Biol. Chem., 269:21191–21197, 1994.PubMedGoogle Scholar
  67. Hammes, H.P., Brownlee, M., Jonczyk, A., Sutter, A., and Preissner, K. Subcutaneous injection of a cyclic peptide antagonist of vitronectin receptor-type integrins inhibits retinal neovascularization. Nature Medicine, 2:529–533, 1996.PubMedCrossRefGoogle Scholar
  68. Hanemaaijer, R., Koolwijk, P., Leclercq, L., De Vree, W. J. A., and Van Hinsbergh, V. W. M. (1993) Regulation of matrix metalloproteinase expression in human vein and microvascular endothelial cells — Effects of tumour necrosis factor-α, interleukin-1 and phorbol ester. Biochem. J., 296:803–809, 1993.PubMedGoogle Scholar
  69. Hébert, C. A., and Baker, J. B. Linkage of extracellular plasminogen activator to fibroblast cytoskeleton: Colocalization of cell surface urokinase with vinculin. J. Cell Biol., 105:1241–1247, 1988.CrossRefGoogle Scholar
  70. Heegaard, C.W., Wiborg Simonsen, A.C., Oka, K., Kjøller, L., Christensen, A., Madsen, B., Ellgaard, L., Chan, L., and Andreasen, P.A. Very low density lipoprotein receptor binds and mediates endocytosis of urokinase-type plasminogen activator-type-1 plasminogen activator inhibitor complex. J. Biol. Chem., 270:20855–20861, 1995.PubMedCrossRefGoogle Scholar
  71. Hobson B. and Denekamp J. Endothelial proliferation in tumours and normal tissues: Continuous labelling studies. Br. J. Cancer, 49:405–413, 1984.PubMedCrossRefGoogle Scholar
  72. Holmes, W.E., Nelles, L., Lijnen, H.R. and Collen, D. Primary structure of human α2-antiplasmin, a serine protease inhibitor (Serpin). J. Biol. Chem., 262:1659–1664, 1987.PubMedGoogle Scholar
  73. Karelina, T.V., Goldberg, G.I., and Eisen, A.Z. Matrix metalloproteinases in blood vessel development in human fetal skin and in cutaneous tumors. J. Invest. Dermatol., 105:411–417, 1995.PubMedCrossRefGoogle Scholar
  74. Keeton, M., Eguchi, Y., Swadey, M., Ahn, C. and Loskutoff, D. Cellular localization of type 1 plasminogen activator inhibitor messenger RNA and protein in murine renal tissue. Am. J. Pathol., 142:59–70, 1993.PubMedGoogle Scholar
  75. Koch, A.E. Polverini, P.J., Kunkel, S.L., Harlow, L.A., DiPietro, L.A., Einer, V.M., Einer S.G., and Strieter, R.M. Interleukin-8 as a macrophage-derived mediator of angiogenesis. Science, 258:1798–1801, 1991.CrossRefGoogle Scholar
  76. Kooistra, T., Schrauwen, Y., and Emeis, J. J. Regulation of endothelial cell t-PA synthesis and release. Int. J. Hematol., 59:233–255, 1994.PubMedGoogle Scholar
  77. Kooistra, T., Bosma, P.J., Toet, K., Cohen, L.H., Griffioen, M., Van den Berg, E., Le Clercq, L., and Van Hinsbergh, V.W.M. Role of protein kinase C and cyclic adenosine monophosphate in the regulation of tissue-type plasminogen activator, plasminogen activator inhibitor-1, and platelet-derived growth factor mRNA levels in human endothelial cells. Possible involvement of proto-oncogenes c-jun and c-fos. Arterioscler. Thrombos., 11:1042–1052, 1991a.CrossRefGoogle Scholar
  78. Kooistra, T., Opdenberg, J.P., Toet, K., Hendriks, H.F.J., Van den Hoogen, R.M., and Emeis, J.J. Stimulation of tissue-type plasminogen activators synthesis by retinoids in cultured human endothelial cells and rat tissues in vivo. Thromb. Haemostas., 65:565–572, 1991b.Google Scholar
  79. Kooistra, T., Toet, K., Kluft, C., Von Voigtlander, P.F., Ennis, M.D., Aiken, J.W., Boadt, J.A. and Erickson, L.A. Triazolobenzodiazepines: a new class of stimulators of tissue-type plasminogen activator synthesis in human endothelial cells. Biochem. Pharmacol. 46:61–67, 1993.PubMedCrossRefGoogle Scholar
  80. Kooistra, T., Lansink, M., Arts, J., Sitter, T., and Toet, K. Involvement of retinoic acid receptor a in the stimulation of tissue-type plasminogen activator gene expression in human endothelial cells. Eur. J. Biochem., 232:425–432, 1995.PubMedCrossRefGoogle Scholar
  81. Koolwijk, P., van Erck, M.G.M., de Vree, W.J.A., Vermeer, M.A., Weich, H.A., Hanemaaijer, R. and van Hinsbergh, V.W.M. Cooperative effect of TNFα, bFGF and VEGF on the formation of tubular structures of human microvascular endothelial cells in a fibrin matrix. Role of urokinase activity. J. Cell Biol., 132:1177–1188,1996.PubMedCrossRefGoogle Scholar
  82. Kwaan, H.C. Tissue fibrinolytic activity studied by a histochemical method. Fed. Proc., 25:52–56, 1966.PubMedGoogle Scholar
  83. Langer, D. J., Kuo, A., Kariko, K., Ahuja, M., Klugherz, B. D., Ivanics, K. M, Hoxie, J. A., Williams, W. V., Liang, B. T., Cines, D. B., and Barnathan, E. S. Regulation of the endothelial cell urokinase-type plasminogen activator receptor — Evidence for cyclic AMP-dependent and protein kinase-C dependent pathways. Circ. Res., 72:330–340, 1993.PubMedCrossRefGoogle Scholar
  84. Lansink, M., and Kooistra, T. Stimulation of tissue-type plasminogen activator expression by retinoic acid in human endothelial cells requires retinoic receptor β2 induction. Blood, 88:531–541, 1996.PubMedGoogle Scholar
  85. Leibovich S.J., Polverini, P.J., Shepard, H.M., Wiseman, D.M., Shively, V. and Nuseir, N. Macrophage-induced angiogenesis is mediated by tumour necrosis factor-α. Nature, 329:630–632, 1987.PubMedCrossRefGoogle Scholar
  86. Levin, E.G., Marotti, K.R., and Santell, L. Protein kinase C and the stimulation of tissue plasminogen activator release from human endothelial cells. Dependence on the elevation of messenger RNA. J. Biol. Chem., 264:16030–16036, 1989.PubMedGoogle Scholar
  87. Liotta, L.A., Steeg, P.S., and Stetler-Stevenson, W.G. Cancer metastasis and angiogenesis — An imbalance of positive and negative regulation. Cell, 64:327–336, 1991.PubMedCrossRefGoogle Scholar
  88. Loskutoff, D.J. Regulation of PAI-1 gene expression. Fibrinolysis, 5:197–206, 1991.Google Scholar
  89. Malek, A.M., Jackman, R., Rosenberg, R.D., Izumo, S. Endothelial expression of thrombomodulin is reversibly regulated by fluid shear stress. Circ. Res., 74:852–860, 1994.PubMedCrossRefGoogle Scholar
  90. Mandriota, S., Seghezzi, G., Vassalli, J-D., Ferrara, N., Wasi, S., Mazzieri, R., Mignatti, P. and Pepper, M. Vascular endothelial growth factor increases urokinase receptor expression in vascular endothelial cells. J. Biol. Chem., 270:9709–9716, 1995.PubMedCrossRefGoogle Scholar
  91. Mignatti, P., Mazzieri, R., and Rifkin, D. B. Expression of the urokinase receptor in vascular endothelial cells is stimulated by basic fibroblast growth factor. J. Cell Biol.,113:1193–1201,1991.PubMedCrossRefGoogle Scholar
  92. Miles, L.A., Levin, E.G., Plescia, J., Collen, D. and Plow, E.F. Plasminogen receptors, urokinase receptors, and their modulation on human endothelial cells. Blood, 72:628–635, 1988.PubMedGoogle Scholar
  93. Miles, L. A., Fless, G. M., Levin, E. G., Scanu, A. M., and Plow, E. F. A potential basis for the thrombotic risks associated with lipoprotein(a). Nature, 399:301–303, 1989a.CrossRefGoogle Scholar
  94. Miles, L. A., Dahlberg, C. M., Levin, E. G., and Plow, E. F. Gangliosides interact directly with plasminogen and urokinase and may mediate binding of these fibrinolytic components to cells. Biochemistry, 28:9337–9343, 1989b.PubMedCrossRefGoogle Scholar
  95. Montesano, R. Regulation of angiogenesis in vitro. Eur. J. Clin. Invest., 22:504–515, 1992.PubMedCrossRefGoogle Scholar
  96. Nachman, R.L. Thrombosis and atherogenesis: molecular connections. Blood, 79:1897–1906, 1992.PubMedGoogle Scholar
  97. Niedbala, M. J., and Stein-Picarella, M. Tumor necrosis factor induction of endothelial cell urokinase-type plasminogen activator mediated proteolysis of extracellular matrix and its antagonism by γ-interferon. Blood, 79:678–687, 1992.PubMedGoogle Scholar
  98. Nikkari S.T., O’Brien, K.D., Ferguson, M., Hatsukami, T., Welgus, H.G., Alpers, C.E., and Clowes, A.W. Interstitial collagenase (MMP-1) expression in human carotid atherosclerosis. Circulation 92:1393–1398, 1995.PubMedCrossRefGoogle Scholar
  99. Nykjær, A., Petersen, C. M., Møller, B., Jensen, P. H., Moestrup, S. K., Holtet, T. L., Etzerodt, M., Thogersen, H. C., Munch, M., Andreasen, P. A., and Gliemann, J. Purified α2-macroglobulin receptor/LDL receptor-related protein binds urokinase activator inhibitor type-1 complex — Evidence that the α2-macroglobulin receptor mediates cellular degradation of urokinase receptor-bound complexes. J. Biol. Chem., 267:14543–14546, 1992.PubMedGoogle Scholar
  100. Odekon, L. E., Sato, Y., and Rifkin, D. B. Urokinase-type plasminogen activator mediates basic fibroblast growth factor-induced bovine endothelial cell migration independent of its proteolytic activity. J. Cell. Physiol., 150:258–263, 1992.PubMedCrossRefGoogle Scholar
  101. Olson, D., Pöllänen, J., Høyer-Hansen, G., Rønne, E., Sakaguchi, K., Wun, T-C., Appella, E., Danø, K. and Blasi, F. Internalization of the urokinase-plasminogen activator inhibitor type-1 complex is mediated by the urokinase receptor. J. Biol. Chem., 267:9129–9133, 1992.PubMedGoogle Scholar
  102. Orth, K., Madison, E. L., Gething, M-J., Sambrook, J. F., and Herz, J. Complexes of tissue-type plasminogen activator and its serpin inhibitor plasminogen-activator inhibitor type-1 are internalized by means of the low density lipoprotein receptor-related protein/α2-macroglobulin receptor. Proc. Natl. Acad. Sci. USA, 89:7422–7426, 1992.PubMedCrossRefGoogle Scholar
  103. Otter, M., Barrett-Bergshoef, M.M. and Rijken, D.C. Binding of tissue-type plasminogen activator by the mannose receptor. J. Biol. Chem. 266:13931–13935, 1991.PubMedGoogle Scholar
  104. Pepper, M. S., Vassalli, J-D., Montesano, R., and Orci, L. Urokinase-type plasminogen activator is induced in migrating capillary endothelial cells. J. Cell Biol., 105:2535–2541, 1987.PubMedCrossRefGoogle Scholar
  105. Pepper, M. S., Belin, D., Montesano, R., Orci, L., and Vassalli, J. Transforming growth factor-β-1 modulates basic fibroblast growth factor induced proteolytic and angiogenic properties of endothelial cells in vitro. J. Cell Biol., 111:743–755, 1990.PubMedCrossRefGoogle Scholar
  106. Pepper, M. S., Ferrara, N., Orci, L., and Montesano, R. Potent synergism between vascular endothelial growth factor and basic fibroblast growth factor in the induction of angiogenesis in vitro. Biochem. Biophys. Res. Commun., 189:824–831, 1992.PubMedCrossRefGoogle Scholar
  107. Pepper, M. S, Sappino, A-P., Stocklin, R., Montesano, R., Orci, L., and Vassalli, J-D. Upregulation of urokinase receptor expression on migrating endothelial cells. J. Cell Biol., 122:673–684, 1993.PubMedCrossRefGoogle Scholar
  108. Pepper, M. S., Vassalli, J-D., Wilks, J. W., Schweigerer, L., Orci, L., and Montesano, R. Modulation of bovine microvascular endothelial cell proteolytic properties of inhibitors of angiogenesis. J. Cell. Biochem., 55:419–434, 1994.PubMedCrossRefGoogle Scholar
  109. Ploplis, V.A., Carmeliet, P., Vazirzadeh, S., Van Vlaenderen, I., Moons, L., Plow, E.F., and Collen, D. Effects of disruption of the plasminogen gene on thrombosis, growth, and health in mice. Circulation, 92:2585–2593, 1995.PubMedCrossRefGoogle Scholar
  110. Ploug, M., Behrendt, N., Lober, D., and Danø, K. Protein structure and membrane anchorage of the cellular receptor for urokinase-type plasminogen activator. Seminars in Thromb. Haemostas., 17:183–193, 1991.CrossRefGoogle Scholar
  111. Plow, E.F., Felez, J. and Miles, L.A. Cellular regulation of fibrinolysis. Thromb. Haemostas., 66:32–36, 1991.Google Scholar
  112. Pöllänen, J., Hedman, K., Nielsen, L. S., Danø, K., and Vaheri, A. Ultrastructural localization of plasma membrane-associated urokinase-type plasminogen activator at focal contacts. J. Cell Biol., 106:87–95, 1988.PubMedCrossRefGoogle Scholar
  113. Polverini, P. Macrophage-induced angiogenesis — A review. Macrophage-Derived Cell Regulatory Factors, 1:54–73, 1989.Google Scholar
  114. Ponfoort, E.D., van Bockel, J.H., and van Hinsbergh, V.W.M. Shear forces induce the synthesis of urokinase-type plasminogen activator in human iliac vein endothelial cells in vitro. Circulation 92 (suppl.) abstract 3016, 1995.Google Scholar
  115. Presta, M., Maier, J. A. M., and Ragnotti, G. The mitogenic signalling pathway but not the plasminogen activator-inducing pathway of basic fibroblast growth factor is mediated through protein kinase C in fetal bovine aortic endothelial cells. J. Cell Biol., 109:1877–1884, 1989.PubMedCrossRefGoogle Scholar
  116. Quax, P. H. A., Van den Hoogen, C. R., Verheijen, J. H., Padro, T., Zeheb, R., Gelehrter, T. D., van Berkel, T. J. C., Kuiper, J., and Emeis, J. J. Endotoxin induction of plasminogen activator and plasminogen activator inhibitor type 1 mRNA in rat tissues in vivo. J. Biol Chem., 265:15560–15563, 1990.PubMedGoogle Scholar
  117. Quax, P.H.A., Koolwijk, P., Verheijen, J.H.M., and Van Hinsbergh, V.W.M. The role of plasminogen activators in vascular pericellular proteolysis. in “Vascular Control of Hemostasis”, V.W.M. van Hinsbergh, ed., pp. 227–245, Harwood Academic Publishers, Amsterdam, 1996.Google Scholar
  118. Quigley, J. P., Gold, L. I., Schwimmer, R., and Sullivan, L. M. Limited cleavage of cellular fibronectin by plasmin activator purified from transformed cells. Proc. Natl Acad. Sci. USA, 84:2776–2780, 1987.PubMedCrossRefGoogle Scholar
  119. Rao, N. K., Shi, G-P., and Chapman, H. A. Urokinase receptor is a multifunctional protein: Influence of receptor occupancy on macrophage gene expression. J. Clin. Invest., 96:465–474, 1995.PubMedCrossRefGoogle Scholar
  120. Rao, J.S., Yamamoto, M., Mohaman, S., Gokaslan, Z.L., Stetler-Stevenson, W.G., Roa, V.H., Liotta, L.A., Nicolson, G.I., and Sawaya, R.E. Expression and localization of 92 kD type IV collagenase genatinase B (MMP-9) in human gliomas. Clin. Exp. Metastasis, 14:12–18, 1996.PubMedCrossRefGoogle Scholar
  121. Redlitz, A., Tan, A. K., Eaton, D. L., and Plow, E. F. Plasma carboxypeptidases as regulators of plasminogen system. J. Clin. Invest., 96:2534–2538, 1995.PubMedCrossRefGoogle Scholar
  122. Resnick N., and Gimbrone M.A. Jr. Hemodynamic forces are complex regulators of endothelial gene expression. FASEB J. 9:874–982, 1995.PubMedGoogle Scholar
  123. Rijken, D. D., Wijngaards, G., and Welbergen, J. Relationship between tissue plasminogen activator and the activators in blood and vascular wall. Thromb. Res., 18:815–830, 1980.PubMedCrossRefGoogle Scholar
  124. Saksela, O.D., Moscatelli, D. and Rifkin, D. The opposing effects of basic fibroblast growth factor and transforming growth factor beta on the regulation of plasminogen activator activity in capillary endothelial cells. J. Cell. Biol. 105:957–963,1987.PubMedCrossRefGoogle Scholar
  125. Sato, H., Takin, T., Okada, Y., Cao, J., Shinagawa, A., Yamamoto, E., and Seiki, M. A matrix metalloproteinase expressed in the surface of invasive tumour cells. Nature, 370:61–65, 1994.PubMedCrossRefGoogle Scholar
  126. Sato, T.N., Tozawa, Y., Deutsch, U., Wolburg-Buchholz, K., Fujiwara, Y., Gendron-Maguire, M., Gridley, T., Wolburg, H., Risau, W. and Qin, Y. Distinct roles of the receptor tyrosine kinases tie-1 and tie-2 in blood vessel formation. Nature, 376:70–74, 1995.PubMedCrossRefGoogle Scholar
  127. Sato, Y., and Rifkin, D. B. Autocrine activities of basic fibroblast growth factor: Regulation of endothelial cell movement, plasminogen activator synthesis, and DNA synthesis. J. Cell Biol., 107:1199–1205, 1988.PubMedCrossRefGoogle Scholar
  128. Schleef, R. R., and Birdwell, C. R. The effect of proteases on endothelial cell migration in vitro. Exp. Cell Res., 141:503–508, 1982.PubMedCrossRefGoogle Scholar
  129. Schleef, R. R., Bevilacqua, M. J., Sawdey, M., Gimbrone, M. A., and Loskutoff, D. J. Cytokine activation of vascular endothelium. Effect on tissue-type plasminogen activator and type 1 plasminogen activator inhibitor. J. Biol. Chem., 263:5797–5803, 1988.PubMedGoogle Scholar
  130. Schrauwen, Y., de Vries, R.E.M., Kooistra T. and Emeis, J.J. Acute release of tissue-type plasminogen activator (t-PA) from the endothelium; regulatory mechanisms and therapeutic target. Fibrinolysis, 8(suppl.2): 8–12, 1994.Google Scholar
  131. Shalaby, F., Rossant, J., Yamaguchi, T.P., Gertsenstein, M., Wu, X-F., Breitman, M.L. and Schuh, A.C. Failure of blood-island formation and vasculogenesis in flk-1-deficient mice. Nature 376:62–66, 1995.PubMedCrossRefGoogle Scholar
  132. Sprengers, E.D. and Kluft, C. Plasminogen activator inhibitors, Blood, 69:381–387, 1987.PubMedGoogle Scholar
  133. Suffredini, A.F., Harpel, P.C. and Parrillo, J.E. Promotion and subsequent inhibition of plasminogen activation after administration of intravenous endotoxin to normal subjects. N. Engl. J. Med. 320:1165–1172, 1989.PubMedCrossRefGoogle Scholar
  134. Thiagarajan, P., Rippon, A.J., and Farrell, D.H. Alternative adhesion sites in human fibrinogen for vascular endothelial cells. Biochemistry, 35:4169–4175, 1996.PubMedCrossRefGoogle Scholar
  135. Thompson, E.A., Nelles, L., and Collen, D. Effect of retinoic acid on the synthesis of tissue-type plasminogen activator and plasminogen activator inhibitor-1 in human endothelial cells. Eur. J. Biochem. 201:627–632, 1991.PubMedCrossRefGoogle Scholar
  136. Thompson, J.A., Anderson, K.D., DiPietro, J.M., Zwiebel, J.A., Zametta, M., Anderson, W.F. and Maciag, T. Site-directed neovessel formation in vivo. Science, 241:1349–1352, 1988.PubMedCrossRefGoogle Scholar
  137. Unemori, E.N., Bouhana, K.S. and Werb, Z. Vectorial secretion of extracellular matrix proteins, matrix-degrading proteinases, and tissue inhibitor of metalloproteinases by endothelial cells. J. Biol Chem., 265:445–451, 1990.PubMedGoogle Scholar
  138. Van Bennekum, A.M., Emeis, J.J., Kooistra, T., and Hendriks, H.F.J. Modulation of tissue-type plasminogen activator by retinoids in rat plasma and tissues. Am. J. Physiol. 264:R931–R937, 1993.PubMedGoogle Scholar
  139. Van den Eijnden-Schrauwen, Y., Kooistra, T., De Vries, R. E. M., and Emeis, J. J. Studies on the acute release of tissue-type plasminogen activator from human endothelial cells in vitro and in rats in vivo: Evidence for a dynamic storage pool. Blood, 85:3510–3517, 1995.PubMedGoogle Scholar
  140. Van Deventer, S.J.H., Büller, H.R., Ten Cate, J.W., Aarden, L.A., Hack, E. and Sturk, A. Experimental endotoxemia in humans: analysis of cytokine release and coagulation, fibrinolytic, and complement pathways. Blood, 76:2520–2526, 1990.PubMedGoogle Scholar
  141. Van Hinsbergh, V. W. M. Impact of endothelial activation on fibrinolysis and local proteolysis in tissue repair. Ann. N. Y. Acad. Sci., 667:151–162, 1992.PubMedCrossRefGoogle Scholar
  142. Van Hinsbergh, V.W.M., Kooistra, T., Van den Berg, E.A., Princen, H.M.G., Fiers, W. and Emeis, J.J. Tumor necrosis factor increases the production of plasminogen activator inhibitor in human endothelial cells in vitro and in rats in vivo. Blood, 72:1467–1473, 1988.PubMedGoogle Scholar
  143. Van Hinsbergh, V. W. M., van den Berg, E. A., Fiers, W., and Dooijewaard, G. Tumor necrosis factor induces the production of urokinase-type plasminogen activator by human endothelial cells. Blood, 75:1991–1998, 1990a.PubMedGoogle Scholar
  144. Van Hinsbergh, V. W. M., Bauer, K. A., Kooistra, T., Kluft, C., Dooijewaard, G., Sherman, M. L., and Nieuwenhuizen, W. Progress of fibrinolysis during tumor necrosis factor infusions in humans Concomitant increase in tissue-type plasminogen activator, plasminogen activator inhibitor type-I, and fibrin(ogen) degradation products. Blood, 76:2284–2289, 1990b.PubMedGoogle Scholar
  145. Van Hinsbergh, V.W.M., Vermeer, M., Koolwijk, P., Grimbergen, J., and Kooistra, T. Genistein reduces tumor necrosis factor α-induced plasminogen activator inhibitor-1 transcription but not urokinase expression in human endothelial cells. Blood, 84:2984–2991, 1994.PubMedGoogle Scholar
  146. Vassalli, J-D. The urokinase receptor. Fibrinolysis, 8:172–181,1994.Google Scholar
  147. Wallén, P. Structure and Function of Tissue Plasminogen Activator and Urokinase, in: “Fundamental and Clinical Fibrinolysis,” P.J. Castellino, P.J. Gaffney, M.M. Samama, and A. Takada, eds., pp. 1–18, Elsevier, Amsterdam, 1987.Google Scholar
  148. Wei, Y., Waltz, D., Rao, N., Drummond, R., Rosenberg, S., and Chapman, H. Identification of the urokinase receptor as cell adhesion receptor for vitronectin. J. Biol Chem., 269:32380–32388, 1994.PubMedGoogle Scholar
  149. Weinberg, J.B., Pippen, A.M.M and Greenberg, C.S. Extravascular fibrin formation and dissolution in synovial tissue of patients with osteoarthitis and rheumatoid arthritis. Arthritis Rheum. 34:996–1005, 1991.PubMedCrossRefGoogle Scholar
  150. Wohlwend, A., Belin, D. and Vassalli, J-D. Plasminogen activator-specific inhibitors produced by human monocytes/macrophages. J. Exp. Med. 165:320–339, 1987.PubMedCrossRefGoogle Scholar
  151. Wun, T-C. and Capuano, A. Spontaneous fibrinolysis in whole human plasma. Identification of tissue activator-related protein as the major plasminogen activator causing spontaneous activity in vitro, J. Biol. Chem. 260:5061–5066, 1985.PubMedGoogle Scholar
  152. Wyne, K.L., Pathak, R.K., Seabra, M.C., and Hobbs, H.H. Expression of the VLDL receptor in endothelial cells. Arterioscl. Thromb. Vasc. Biol., 16:407–415, 1996.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Victor W. M. van Hinsbergh
    • 1
  • Pieter Koolwijk
    • 1
  • Erik Ponfoort
    • 1
  • Roeland Hanemaaijer
    • 1
  • Jef. J. Emeis
    • 1
  • Teake Kooistra
    • 1
  • Paul H. A. Quax
    • 1
  1. 1.Gaubius Laboratory TNO-PGLeidenThe Netherlands

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