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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References
Utermann, G. Science 246, 904–910 (1989).
Genest, J. et al. Circulation 85, 2025–2033 (1992).
Schreiner, P. et al. Arterioscl. Thromb. 13, 826–833 (1993).
McLean, J. W. et al. Nature 330, 132–137 (1987).
Grainger, D. J. et al. Science 260, 1655–1659 (1993).
Kirschenlohr, H. L., Metcalfe, J. C., Weissberg, P. L. & Grainger, D. J. Am. J. Physiol. 265, C571–C576 (1993).
Lawn, R. M., Wade, D. P., Hammer, R. E., Verstuyft, J. G. & Rubin, E. M. Nature 360, 670–672 (1992).
Chiesa, G. et al. J. biol. Chem. 267, 24369–24374 (1992).
Rath, M. et al. Arteriosclerosis 9, 579–592 (1989).
Cushing, G. L. et al. Arteriosclerosis 9, 593–603 (1989).
Kreutzer, J. et al. Chem. Phys. Lipids 67/68, 175–190 (1994).
Miles, L. A. & Plow, E. F. Thromb. Haemostasis 63, 331–335 (1990).
Kojima, S., Harpel, P. C. & Rifkin, D. B. J. Cell Biol. 113, 1439–1445 (1991).
Massague, J. A. Rev. Cell Biol. 6, 597–641 (1990).
Shanahan, C. M., Weissberg, P. L. & Metcalfe, J. C. Circ. Res. 73, 193–204 (1993).
Giacelli, C., Bae, N., Lombardi, D., Majesky, M. & Schwartz, S. Biochem. biophys. Res. Commun. 177, 867–873 (1991).
Giacelli, C. M. et al. J. clin. Invest. 92, 1686–1696 (1993).
Gadeau, A. P., Campan, M., Millet, D., Candresse, T. & Desgranges, C. Arterioscl. Thromb. 13, 120–125 (1993).
O'Brien, E. R. et al. Circ. Res. 73, 223–231 (1993).
Campbell, J. H., Reardon, M. F., Campbell, G. R. & Nestel, P. J. Arteriosclerosis 5, 318–324 (1985).
Rinderknecht, H. Experientia 16, 430–436 (1960).
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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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DOI: https://doi.org/10.1038/370460a0
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