Pericyte adhesion is impaired on extracellular matrix produced by endothelial cells in high hexose concentrations.
OBJECTIVE
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
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.
Beltramo
E
E
Department of Internal Medicine, University of Turin, Torino, Italy. elena.beltramo@unito.it
Pomero
F
F
Allione
A
A
D'Alù
F
F
Ponte
E
E
Porta
M
M
D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D003930:Diabetic Retinopathy / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005109:Extracellular Matrix / Q000187:drug effects / Q000502:physiology*; D005690:Galactose / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D006601:Hexoses / Q000494:pharmacology*; D006801:Humans; D020286:Pericytes / Q000187:drug effects / Q000502:physiology*; D013237:Stereoisomerism; D014470:Umbilical Cord
D006601:Hexoses; D005947:Glucose; D005690:Galactose