Glyoxalase-1 overexpression partially prevents diabetes-induced impaired arteriogenesis in a rat hindlimb ligation model

Glycoconj J. 2016 Aug;33(4):627-30. doi: 10.1007/s10719-016-9681-3. Epub 2016 Jun 13.

Abstract

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.

Keywords: Advanced glycation end-products; Arteriogenesis; Diabetes; Glyoxalase-I; Magnetic resonance angiography.

MeSH terms

  • Animals
  • Diabetes Mellitus, Experimental* / enzymology
  • Diabetes Mellitus, Experimental* / genetics
  • Diabetic Angiopathies* / enzymology
  • Diabetic Angiopathies* / genetics
  • Diabetic Angiopathies* / prevention & control
  • Gene Expression Regulation, Enzymologic*
  • Hindlimb / blood supply*
  • Hindlimb / enzymology
  • Hindlimb / pathology
  • Lactoylglutathione Lyase / biosynthesis*
  • Lactoylglutathione Lyase / genetics
  • Neovascularization, Pathologic* / enzymology
  • Neovascularization, Pathologic* / genetics
  • Neovascularization, Pathologic* / prevention & control
  • Rats
  • Rats, Transgenic

Substances

  • Lactoylglutathione Lyase