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Antifibrinolytic activity of apolipoprotein(a) in vivo: Human apolipoprotein(a) transgenic mice are resistant to tissue plasminogen activator-mediated thrombolysis

Nature Medicine volume 1, pages 256–259 (1995)Cite this article

An Erratum to this article was published on 01 June 1995

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Abstract

The extensive homology between apolipoprotein(a) and plasminogen has led to the hypothesis that the increased risk for atherosclerosis, cardiac disease and stroke associated with elevated levels of apolipoprotein(a) may reflect modulation of fibrinolysis. We have investigated the role of apolipoprotein(a) on clot lysis in transgenic mice expressing the human apolipoprotein(a) gene. These mice develop fatty streak lesions resembling early lesions of human atherosclerosis. Pulmonary emboli were generated in mice by injection, through the right jugular vein, of a human platelet-rich plasma clot radiolabelled with technetium-99m-labelled antifibrin antibodies. Tissue plasminogen activator was introduced continuously via the right jugular vein. Clot lysis, determined by ex vivo imaging, was depressed in mice carrying the apolipoprotein(a) transgene relative to their sex-matched normal littermates. These results directly demonstrate an in vivo effect of apolipoprotein(a) on fibrinolysis, an effect that may contribute to the pathology associated with elevated levels of this protein.

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  • 01 June 1995

    HIV-speciflc cytotoxic T-cells in HIV-exposed but uninfected Gambian women S. Rowland-Jones, J. Sutton, K. Ariyoshi, T. Dong, F. Gotch, S. Mcadam, D. Whitby, S. Sabally, A. Gallimore, T. Corrah, M. Takiguchi, T. Schultz, Andrew Mcmichael & H. Whittle Nature Medicine 1, 59–64, 1995. An error in typography resulted in the incorrect printing of m for the Greek character μ.

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Author notes

  1. Barbara C. Furie: Correspondence should be addressed to B.C.F.

Authors and Affiliations

  1. Division of Cardiology, New England Medical Center, 750 Washington Street, NEMC #70, Boston, Massachusetts, 02111, USA

    Theresa M. Palabrica & Mark J. Aronovitz

  2. the Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts, 02111, USA

    Theresa M. Palabrica & Mark J. Aronovitz

  3. Falk Cardiovascular Research Center, Division of Cardiovascular Medicine, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, California, 94305, USA

    Alexander C. Liu & Richard M. Lawn

  4. Center for Hemostasis and Thrombosis Research, Division of Hematology-Oncology, New England Medical Center, 750 Washington Street, NEMC #832, Boston, Massachusetts, 02111, USA

    Bruce Furie & Barbara C. Furie

  5. the Departments of Medicine and Biochemistry, Tufts University School of Medicine, Boston, Massachusetts, 02111, USA

    Barbara C. Furie

Authors
  1. Theresa M. Palabrica
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  2. Alexander C. Liu
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  3. Mark J. Aronovitz
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  4. Bruce Furie
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  5. Richard M. Lawn
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  6. Barbara C. Furie
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Palabrica, T., Liu, A., Aronovitz, M. et al. Antifibrinolytic activity of apolipoprotein(a) in vivo: Human apolipoprotein(a) transgenic mice are resistant to tissue plasminogen activator-mediated thrombolysis. Nat Med 1, 256–259 (1995). https://doi.org/10.1038/nm0395-256

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