AIMS/HYPOTHESIS: Thickening of the basement membrane and selective loss of pericytes are early events in diabetic retinopathy. We aimed at checking whether pericyte interaction with extracellular matrix produced by endothelial cells is influenced by the hexose concentrations in which endothelial cells are cultured. METHODS: Conditioned extracellular matrixes were obtained by growing human umbilical vein endothelial cells in media containing 28 mmol/l hexoses (D-glucose, D-galactose, L-glucose), which undergo different intracellular processing, before and after adding the inhibitors of protein glycation thiamine or aminoguanidine. Having removed the endothelium, bovine retinal pericytes were grown on such matrixes and, in separate experiments, on laminin, fibronectin or type IV collagen. Pericyte adhesion was determined by cell counts 18 h after seeding. RESULTS: Reduced adhesion was observed on matrixes produced in high D-glucose, high D-galactose and high L-glucose. Both thiamine and aminoguanidine restored impaired pericyte adhesion when added to high D-glucose and high D-galactose, but not L-glucose. Laminin, fibronectin and type IV collagen did not consistently modify pericyte adhesion. CONCLUSIONS/INTERPRETATIONS: Pericyte adhesion is impaired on extracellular matrix produced by endothelium in high hexose concentrations. This could result from excess protein glycation, corrected by aminoguanidine and thiamine, rather than altered glycoprotein composition.
AIMS/HYPOTHESIS: Thickening of the basement membrane and selective loss of pericytes are early events in diabetic retinopathy. We aimed at checking whether pericyte interaction with extracellular matrix produced by endothelial cells is influenced by the hexose concentrations in which endothelial cells are cultured. METHODS: Conditioned extracellular matrixes were obtained by growing human umbilical vein endothelial cells in media containing 28 mmol/l hexoses (D-glucose, D-galactose, L-glucose), which undergo different intracellular processing, before and after adding the inhibitors of protein glycation thiamine or aminoguanidine. Having removed the endothelium, bovine retinal pericytes were grown on such matrixes and, in separate experiments, on laminin, fibronectin or type IV collagen. Pericyte adhesion was determined by cell counts 18 h after seeding. RESULTS: Reduced adhesion was observed on matrixes produced in high D-glucose, high D-galactose and high L-glucose. Both thiamine and aminoguanidine restored impaired pericyte adhesion when added to high D-glucose and high D-galactose, but not L-glucose. Laminin, fibronectin and type IV collagen did not consistently modify pericyte adhesion. CONCLUSIONS/INTERPRETATIONS: Pericyte adhesion is impaired on extracellular matrix produced by endothelium in high hexose concentrations. This could result from excess protein glycation, corrected by aminoguanidine and thiamine, rather than altered glycoprotein composition.
Authors: F Pomero; A Allione; E Beltramo; S Buttiglieri; F D'Alù; E Ponte; A Lacaria; M Porta Journal: Diabetologia Date: 2003-03-01 Impact factor: 10.122
Authors: A W Stitt; S-J Hughes; P Canning; O Lynch; O Cox; N Frizzell; S R Thorpe; T G Cotter; T M Curtis; T A Gardiner Journal: Diabetologia Date: 2004-10-22 Impact factor: 10.122
Authors: Michèle Geoffrion; Xueliang Du; Zehra Irshad; Barbara C Vanderhyden; Kerri Courville; Guangzhi Sui; Vivette D D'Agati; Sylvie Ott-Braschi; Naila Rabbani; Paul J Thornalley; Michael Brownlee; Ross W Milne Journal: Physiol Rep Date: 2014-06-11