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Aminosalicylic acid reduces the antiproliferative effect of hyperglycaemia, advanced glycation endproducts and glycated basic fibroblast growth factor in cultured bovine aortic endothelial cells: Comparison with aminoguanidine

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Abstract

Hyperglycaemia reduces proliferation of bovine aortic endothelial cells in vitro. A similar effect in vivo may contribute to long-term complications of diabetes such as impaired wound-healing and retinopathy.

We report the effect of increased glucose concentrations, glycated basic fibroblast growth factor (FGF-2) and bovine serum albumin-derived advanced glycation endproducts (BSA-AGE) on the proliferation of bovine aortic endothelial cells.

Glucose (30 and 50 mmol/l) had an antiproliferative effect on endothelial cells. This effect may be mediated through reduced mitogenic activity of FGF-2. The glycation of FGF-2 with 250 mmol/l glucose-6-phosphate led to reduced mitogenic activity compared to native FGF-2. BSA-AGE at concentrations of 10, 50 and 250 μg/ml had an antiproliferative effect on cultured endothelial cells.

Aminosalicylic acid at a concentration of 200 μmol/l proved to be more effective than equimolar concentrations of aminoguanidine in protecting endothelial cells against the antiproliferative effects of both high (30 mmol/l) glucose and 50 μg/ml BSA-AGE. FGF-2 glycated in the presence of 4 mmol/l aminosalicylic acid or aminoguanidine retained mitogenic activity compared to that glycated in their absence.

Compounds like aminoguanidine and, in particular, aminosalicylic acid protect endothelial cells against glucose-mediated toxicity and may therefore have therapeutic potential.

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Authors and Affiliations

  1. Department of Biological Sciences, Manchester Metropolitan University, Chester Street, Manchester, M1 5GD, UK

    Yasotha Duraisamy, John Gaffney, Mark Slevin, Christopher A. Smith & Nessar Ahmed

  2. Department of Chemistry and Materials, Manchester Metropolitan University, Chester Street, Manchester, M1 5GD, UK

    Kenneth Williamson

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  1. Yasotha Duraisamy
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Duraisamy, Y., Gaffney, J., Slevin, M. et al. Aminosalicylic acid reduces the antiproliferative effect of hyperglycaemia, advanced glycation endproducts and glycated basic fibroblast growth factor in cultured bovine aortic endothelial cells: Comparison with aminoguanidine. Mol Cell Biochem 246, 143–153 (2003). https://doi.org/10.1023/A:1023470921116

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