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Lipoprotein(a) modulation of endothelial cell surface fibrinolysis and its potential role in atherosclerosis

Nature volume 339, pages 303–305 (1989)Cite this article

Abstract

ENDOTHELIAL cells play a critical role in thromboregulation by virtue of a surface-connected fibrinolytic system. Cultured endothelial cells synthesize and secrete tissue-type plasminogen activator (t-PA)1 which can bind to at least two discrete sites on the cell surface2–4. These binding sites preserve the catalytic activity of t-PA and protect it from its physiological inhibitor (PAI-1)2. N-terminal glutamic acid plasminogen (Glu-PLG), the main circulating fibrinolytic zymogen, also interacts specifically with the endothelial cell surface5,6. Binding is associated with a 12-fold increase in catalytic efficiency of plasmin generation by t-PA5 which may reflect conversion of Glu-PLG to its plasmin-modified form, N-terminal lysine plasminogen (Lys-PLG)7. Lipoprotein(a) is an atherogenic8–11 lipoprotein particle which contains the plasminogen-like12,13apolipoprotein(a) bound to low density lipoprotein. We report here that lipoprotein(a) interferes with endothelial cell fibrinolysis by inhibiting plasminogen binding and hence plasmin generation. In addition, we demonstrate lipoprotein(a) accumulation in atherosclerotic lesions. These findings may provide a link between impaired cell surface fibrinolysis and progressive atherosclerosis.

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References

  1. Levin, E. G. & Luskotoff, D. J. J. Cell Biol. 94, 631–636 (1982).

    Article  CAS  Google Scholar 

  2. Hajjar, K. A., Hamel, N. M., Harpel, P. C. & Nachman, R. L. J. clin. Invest. 80, 1712–1719 (1987).

    Article  CAS  Google Scholar 

  3. Beebe, D. P. Thromb. Res. 46, 241–254 (1987).

    Article  CAS  Google Scholar 

  4. Barnathan, E. S. et al. J. biol. Chem. 263, 7792–7799 (1988).

    CAS  PubMed  Google Scholar 

  5. Hajjar, K. A., Harpel, P. C., Jaffe, E. A. & Nachman, R. L. J. biol. Chem. 261, 11656–11662 (1986).

    CAS  PubMed  Google Scholar 

  6. Miles, L. A., Levin, E. G., Plescia, J., Collen, D. & Plow, E. F. Blood 72, 628–635 (1988).

    CAS  Google Scholar 

  7. Hajjar, K. A. & Nachman, R. L. J. clin. Invest. 82, 1769–1778 (1988).

    Article  CAS  Google Scholar 

  8. Dahlen, G., Frick, M. H., Berg, K., Valle, M. & Wiljasalo, M. Clin. Genetics 8, 183–189 (1975).

    Article  CAS  Google Scholar 

  9. Armstrong, V. W. et al. Atherosclerosis 62, 249–257 (1986).

    Article  CAS  Google Scholar 

  10. Rhoads, G. G., Morton, N. E., Gulbrandsen, C. L. & Kagan A. Am. J. Epidemiol. 108, 350–356 (1978).

    Article  CAS  Google Scholar 

  11. Hoff, H. F. et al. Circulation 77, 1238–1244 (1988).

    Article  CAS  Google Scholar 

  12. Eaton, D. L. et al. Proc. natn. Acad. Sci. U.S.A. 84, 3224–3228 (1987).

    Article  ADS  CAS  Google Scholar 

  13. McLean, J. W. et al. Nature 330, 132–137 (1987).

    Article  ADS  CAS  Google Scholar 

  14. Scanu, A. M. Sem. Thromb. Hemost 14, 266–270 (1988).

    Article  CAS  Google Scholar 

  15. Gaubatz, J. W., Heideman, C., Gotto, A. M., Morrisett, J. D. & Dahlen, G. H. J. biol. Chem. 254, 4582–4589 (1983).

    Google Scholar 

  16. Utermann, G. & Weber, W. FEBS Lett. 154, 357–361 (1983).

    Article  CAS  Google Scholar 

  17. Fless, G. M., Rolih, C. A. & Scanu, A. M. J. biol. Chem. 259, 11470–11478 (1984).

    CAS  PubMed  Google Scholar 

  18. Weitkamp, L. R., Guttormsen, S. A. & Schultz, J. S. Hum. Genet. 79, 80–82 (1988).

    Article  CAS  Google Scholar 

  19. Munson, P. J. & Rodbard, D. Analyt. Biochem. 107, 220–239 (1980).

    Article  CAS  Google Scholar 

  20. Groener, J. E. M. & Kostner, G. M. J. Lipid Res. 28, 1053–1056 (1987).

    CAS  PubMed  Google Scholar 

  21. Albers, J. J., Adolphson, J. L. & Hazzard, W. R. J. Lipid Res. 18, 331–338 (1977).

    CAS  PubMed  Google Scholar 

  22. Utermann, G., Kraft, H. G., Menzel, H. J., Hopferwisser, T. & Seitz, C. Hum. Genet. 78, 41–46 (1988).

    Article  CAS  Google Scholar 

  23. Gonzalez-Gronow, M., Edelberg, J. M. & Pizzo, S. M. Biochemistry 28, 2374–2377 (1989).

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pediatrics, Cornell University Medical College, 1300 York Avenue, New York, New York, 10021, USA

    Katherine A. Hajjar

  2. Department of Medicine, Cornell University Medical College, 1300 York Avenue, New York, New York, 10021, USA

    Katherine A. Hajjar & Ralph L. Nachman

  3. Laboratory of Biochemical Genetics and Metabolism, Rockefeller University, 1230 York Avenue, New York, New York, 10021-6399, USA

    Dov Gavishi & Jan L. Breslow

Authors
  1. Katherine A. Hajjar
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  2. Dov Gavishi
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  3. Jan L. Breslow
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  4. Ralph L. Nachman
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Hajjar, K., Gavishi, D., Breslow , J. et al. Lipoprotein(a) modulation of endothelial cell surface fibrinolysis and its potential role in atherosclerosis. Nature 339, 303–305 (1989). https://doi.org/10.1038/339303a0

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