Glyoxalase-1 overexpression partially prevents diabetes-induced impaired arteriogenesis in a rat hindlimb ligation model.
We hypothesize that diabetes-induced impaired collateral formation after a hindlimb ligation in rats is in part caused by intracellular glycation and that overexpression of glyoxalase-I (GLO-I), i.e. the major detoxifying enzyme for advanced-glycation-endproduct (AGE) precursors, can prevent this. Wild-type and GLO-I transgenic rats with or without diabetes (induced by 55 mg/kg streptozotocin) were subjected to ligation of the right femoral artery. Laser Doppler perfusion imaging showed a significantly decreased blood perfusion recovery after 6 days in the diabetic animals compared with control animals, without any effect of Glo1 overexpression. In vivo time-of-flight magnetic resonance angiography at 7-Tesla showed a significant decrease in the number and volume of collaterals in the wild-type diabetic animals compared with the control animals. Glo1 overexpression partially prevented this decrease in the diabetic animals. Diabetes-induced impairment of arteriogenic adaptation can be partially rescued by overexpressing of GLO-I, indicating a role of AGEs in diabetes-induced impaired collateral formation.
Department of Internal Medicine, Laboratory for Metabolism and Vascular Medicine, Maastricht University Medical Center, P.O. Box 5800, 6202, AZ, Maastricht, The Netherlands.
Olaf
O
Brouwers
Department of Internal Medicine, Laboratory for Metabolism and Vascular Medicine, Maastricht University Medical Center, P.O. Box 5800, 6202, AZ, Maastricht, The Netherlands.
Liang
L
Yu
Department of Internal Medicine, Laboratory for Metabolism and Vascular Medicine, Maastricht University Medical Center, P.O. Box 5800, 6202, AZ, Maastricht, The Netherlands.
Petra
P
Niessen
Department of Radiology, Maastricht University Medical Centre, Universiteitssingel 50, Maastricht, the Netherlands.
Jos
J
Slenter
Department of Radiology, Maastricht University Medical Centre, Universiteitssingel 50, Maastricht, the Netherlands.
Karolien
K
Jaspers
Department of Physiology, Maastricht University Medical Centre, Universiteitssingel 50, Maastricht, the Netherlands.
Allard
A
Wagenaar
Department of Physiology, Maastricht University Medical Centre, Universiteitssingel 50, Maastricht, the Netherlands.
Mark
M
Post
Centre of Translational and Advanced Research, Tohoku University, Sendai, Miyagi Prefecture, 980-8577, Japan.
Toshio
T
Miyata
Department of Radiology, Maastricht University Medical Centre, Universiteitssingel 50, Maastricht, the Netherlands.
Walter
W
Backes
Department of Internal Medicine, Laboratory for Metabolism and Vascular Medicine, Maastricht University Medical Center, P.O. Box 5800, 6202, AZ, Maastricht, The Netherlands.
Coen
C
Stehouwer
Department of Internal Medicine, Laboratory for Metabolism and Vascular Medicine, Maastricht University Medical Center, P.O. Box 5800, 6202, AZ, Maastricht, The Netherlands.
Maya
M
Huijberts
Department of Internal Medicine, Laboratory for Metabolism and Vascular Medicine, Maastricht University Medical Center, P.O. Box 5800, 6202, AZ, Maastricht, The Netherlands. c.schalkwijk@maastrichtuniversity.nl.
Casper
C
Schalkwijk
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000235:genetics; D003925:Diabetic Angiopathies / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control; D015971:Gene Expression Regulation, Enzymologic; D006614:Hindlimb / Q000098:blood supply* / Q000201:enzymology / Q000473:pathology; D007791:Lactoylglutathione Lyase / Q000096:biosynthesis* / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control; D051381:Rats; D055647:Rats, Transgenic
D007791:Lactoylglutathione Lyase
Advanced glycation end-products; Arteriogenesis; Diabetes; Glyoxalase-I; Magnetic resonance angiography