Activation of transforming growth factor-β is inhibited in transgenic apolipoprotein(a) mice (original) (raw)

Nature volume 370, pages 460–462 (1994)Cite this article

Abstract

A HIGH concentration of serum lipoprotein(a) is a risk factor for atherosclerosis1–3. Lipoprotein(a) consists of low-density lipoprotein with the additional protein component, apolipoprotein(a), a homologue of plasminogen4. Lipoprotein(a) and apolipoprotein(a) enhance proliferation of human vascular smooth muscle cells (hVSMCs) in culture by inhibiting activation of plasminogen to plasmin, thus blocking the proteolytic activation of transforming growth factor-β (TGF-β)5, an autocrine inhibitor of hVSMC proliferation5,6. The hypothesis that this pathway is a key step in atherogenesis5 is tested on transgenic mice expressing the human apolipoprotein(a) gene. We show here that the activation of TGF-β is inhibited in the aortic wall and serum of mice expressing apolipoprotein(a), as a consequence of apolipoprotein(a) inhibition of plasminogen activation. These effects are closely correlated with VSMC activation.

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Author notes

  1. Alexander C. Liu and Richard M. Lawn: Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, California 94305, USA

Authors and Affiliations

  1. Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QW, UK
    David J. Grainger, Paul R. Kemp, Alexander C. Liu, Richard M. Lawn & James C. Metcalfe

Authors

  1. David J. Grainger
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  2. Paul R. Kemp
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  3. Alexander C. Liu
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  4. Richard M. Lawn
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  5. James C. Metcalfe
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Grainger, D., Kemp, P., Liu, A. et al. Activation of transforming growth factor-β is inhibited in transgenic apolipoprotein(a) mice.Nature 370, 460–462 (1994). https://doi.org/10.1038/370460a0

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