Reversal of Hyperglycemia-Induced Angiogenesis Deficit of Human Endothelial Cells by Overexpression of Glyoxalase 1In Vitro

Authors

  • Usman Ahmed,

    1. Department of Biological Sciences, University of Essex, Colchester, United Kingdom
    2. Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry, United Kingdom
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  • Darin Dobler,

    1. Department of Biological Sciences, University of Essex, Colchester, United Kingdom
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  • Sarah J. Larkin,

    1. Department of Biological Sciences, University of Essex, Colchester, United Kingdom
    2. Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry, United Kingdom
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  • Naila Rabbani,

    1. Department of Biological Sciences, University of Essex, Colchester, United Kingdom
    2. Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry, United Kingdom
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  • Paul J. Thornalley

    1. Department of Biological Sciences, University of Essex, Colchester, United Kingdom
    2. Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry, United Kingdom
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Address for correspondence: Paul J. Thornalley, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry CV2 2DX, UK. Voice: +4424 7696 8594; fax +4424 7696 8595.
 P.J.Thornalley@warwick.ac.uk

Abstract

Dicarbonyl glycation of RGD and GFOGER sites in type IV collagen has been associated with decreased angiogenesis. In this study, we investigated whether overexpression of glyoxalase 1 to decrease dicarbonyl glycation would prevent the angiogenesis deficit induced by hyperglycemia in vitro. Transfection of human microvascular endothelial cells resulted in a four-fold increase in glyoxalase 1 activity compared with controls. Incubation of human microvascular endothelial cells in model hyperglycemia produced a 32% decrease in formation of tube structures that was prevented by glyoxalase 1 overexpression. We conclude that increased protection against dicarbonyl glycation of endothelial cell protein protects hyperglycemia-induced angiogenesis deficit.

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