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Receptor for advanced glycation end products (RAGE) deficiency attenuates the development of atherosclerosis in

Aino Soro-Paavonen1, Anna M D Watson, Jiaze Li

  • 1Albert Einstein Juvenile Diabetes Research Foundation Centre for Diabetes Complications, Diabetes Metabolism Division, Baker Heart Research Institute, Melbourne, Australia.

Diabetes
|May 31, 2008
PubMed
Abstract

Insights

Deleting the receptor for advanced glycation end products (RAGE) significantly reduced atherosclerosis in diabetic mice. This highlights RAGE as a key factor in diabetic vascular disease and a potential therapeutic target.

Area of Science:

  • Vascular Biology
  • Diabetic Complications
  • Atherosclerosis Research

Background:

  • Receptor for advanced glycation end products (RAGE) activation is implicated in diabetic vasculature and atherogenesis.
  • Diabetic macrovascular complications represent a significant health burden.

Purpose of the Study:

  • To investigate the role of RAGE in the development of atherosclerosis in a diabetic mouse model.
  • To assess the therapeutic potential of targeting RAGE in diabetic atherosclerosis.

Main Methods:

  • Utilized a diabetic apolipoprotein E knockout (apoE-/-) mouse model.
  • Generated RAGE-/-/apoE-/- double knockout mice and induced diabetes using streptozotocin.
  • Assessed atherosclerotic plaque accumulation after 20 weeks.

Main Results:

  • Diabetic RAGE-/-/apoE-/- mice exhibited significantly reduced atherosclerotic plaque area compared to diabetic apoE-/- mice.
  • RAGE deletion attenuated leukocyte recruitment, decreased proinflammatory mediators (NF-κB, VCAM-1, MCP-1), and reduced oxidative stress.
  • RAGE and its ligands (S100A8/A9, HMGB1, AGEs) were elevated in plaques of diabetic apoE-/- mice.

Conclusions:

  • RAGE plays a pivotal role in accelerated atherosclerosis associated with diabetes.
  • Targeting RAGE activation may offer a promising strategy for preventing and treating diabetic macrovascular complications.

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