Reversal of hyperglycemia-induced angiogenesis deficit of human endothelial cells by overexpression of glyoxalase 1 in vitro.
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.
Ahmed
Usman
U
Department of Biological Sciences, University of Essex, Colchester, United Kingdom.
Dobler
Darin
D
Larkin
Sarah J
SJ
Rabbani
Naila
N
Thornalley
Paul J
PJ
D004730:Endothelium, Vascular / Q000201:enzymology*; D006801:Humans; D006943:Hyperglycemia / Q000150:complications*; D007700:Kinetics; D007791:Lactoylglutathione Lyase / Q000235:genetics / Q000378:metabolism*; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D009389:Neovascularization, Pathologic / Q000209:etiology* / Q000517:prevention & control*; D014162:Transfection
D007791:Lactoylglutathione Lyase