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.
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 microg/ml had an antiproliferative effect on cultured endothelial cells. Aminosalicylic acid at a concentration of 200 micromol/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 microg/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.
Duraisamy
Yasotha
Y
Department of Biological Sciences, Manchester Metropolitan University, Chester Street, Manchester, UK.
Gaffney
John
J
Slevin
Mark
M
Smith
Christopher A
CA
Williamson
Kenneth
K
Ahmed
Nessar
N
D000636:Aminosalicylic Acids / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D017127:Glycation End Products, Advanced / Q000378:metabolism / Q000494:pharmacology; D006031:Glycosylation; D006146:Guanidines / Q000494:pharmacology*
D000636:Aminosalicylic Acids; D017127:Glycation End Products, Advanced; D006146:Guanidines; D016222:Fibroblast Growth Factor 2; D005947:Glucose; C004479:pimagedine