Advanced glycation end product interventions reduce diabetes-accelerated atherosclerosis

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Published on: February 28, 2013

Josephine M Forbes1, Louis Teo Loon Yee, Vicki Thallas

  • 1Danielle Alberti Memorial Centre for Diabetes Complications, Vascular Division, Wynn Domain, Baker Medical Research Institute, Melbourne, Australia. josephine.forbes@baker.edu.au

Diabetes
|June 29, 2004
PubMed

Insights

Advanced glycation end products (AGEs) contribute to atherosclerosis in diabetes. Treatments with ALT-711 or aminoguanidine (AG) reduced AGEs and attenuated plaque development in diabetic mice.

Area of Science:

  • Biomedical science
  • Cardiovascular research
  • Diabetes complications

Background:

  • Advanced glycation end product (AGE) formation is implicated in atherosclerosis progression, especially in diabetic patients.
  • Diabetes exacerbates atherosclerosis, partly due to AGE accumulation and associated vascular changes.

Purpose of the Study:

  • To investigate the effects of an AGE cross-link breaker (ALT-711) and an AGE formation inhibitor (aminoguanidine, AG) on atherosclerosis in a diabetic mouse model.
  • To assess the impact of these treatments on AGE accumulation, collagen content, and profibrotic markers in the aorta.

Main Methods:

  • Streptozotocin-induced diabetic apolipoprotein E-deficient (apoE-/-) mice were treated for 20 weeks with no treatment, ALT-711, or AG.
  • Atherosclerotic plaque area, AGE levels, collagen solubility, collagen types I, III, and IV, and profibrotic markers were quantified in aortas and plasma.

Main Results:

  • Both ALT-711 and AG significantly attenuated the diabetes-induced increase in aortic plaque area, particularly in the thoracic and abdominal aortas.
  • Treatments ameliorated diabetes-associated AGE accumulation in aortas and plasma, reduced skin collagen cross-linking, and decreased the vascular receptor for AGE.
  • Aortic collagen content and levels of transforming growth factor-beta and connective tissue growth factor were reduced by both treatments in diabetic mice.

Conclusions:

  • ALT-711 and aminoguanidine effectively reduce vascular AGE accumulation and attenuate atherosclerosis in diabetic mice.
  • These findings highlight the therapeutic potential of targeting AGEs to manage atherosclerosis in diabetes.

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