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Glycated albumin modified by amadori adducts modulates aortic endothelial cell biology

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Abstract

Increased protein glycation has been mechanistically linked to accelerated vascular pathobiology in diabetes. To test the influence of protein modified by Amadori glucose adducts on vascular cell biology, we examined the effect of glycated albumin on replicative capacity and basement membrane collagen production by aortic endothelial cells in culture. Relative to carbohydrate-free albumin, which supported cell proliferation and Type IV collagen synthesis, glycated albumin significantly inhibited3H-thymidine incorporation and Type IV collagen production. The glycated albumin-induced effects were prevented by monoclonal antibodies (A717) that specifically react with Amadori-modified albumin, but not by IgG that was unreactive with glycated albumin. A717 had no effect on thymidine incorporation or collagen synthesis by cells cultured in the presence of nonglycated albumin. The findings indicate that the interaction of glycated albumin with endothelial cells, which have been shown to display dose-responsive, saturable receptors, limits cell replication and triggers maladaptive biosynthetic programs, which may contribute to degenerative macrovascular disease in diabetes.

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Authors and Affiliations

  1. Department of Biochemistry, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Margo P. Cohen

  2. Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Fuad N. Ziyadeh

  3. Penn Center for Molecular Studies of Kidney Diseases, Philadelphia, Pennsylvania, USA

    Fuad N. Ziyadeh

  4. University City Science Center, Philadelphia, Pennsylvania, USA

    Elizabeth Hud & Van-Yu Wu

Authors
  1. Margo P. Cohen
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  2. Elizabeth Hud
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  3. Van-Yu Wu
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  4. Fuad N. Ziyadeh
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Cohen, M.P., Hud, E., Wu, VY. et al. Glycated albumin modified by amadori adducts modulates aortic endothelial cell biology. Mol Cell Biochem 143, 73–79 (1995). https://doi.org/10.1007/BF00925929

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  • DOI: https://doi.org/10.1007/BF00925929

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