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Suppression of accelerated diabetic atherosclerosis by the soluble receptor for advanced glycation endproducts

L Park1, K G Raman, K J Lee

  • 1Department of Surgery, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA.

Nature Medicine
|September 12, 1998
PubMed

Insights

Diabetic atherosclerosis, a complication unresponsive to blood sugar control, involves advanced glycation endproducts (AGEs). Blocking the AGE receptor significantly reduced this condition in diabetic mice, suggesting a new therapeutic target.

Area of Science:

  • Cardiovascular Research
  • Endocrinology
  • Molecular Medicine

Background:

  • Accelerated atherosclerosis in diabetes contributes significantly to patient morbidity and mortality.
  • Conventional therapies targeting euglycemia are often ineffective against diabetic macrovascular complications.
  • Hyperglycemia promotes protein and lipid glycation, leading to advanced glycation endproducts (AGEs) accumulation.

Purpose of the Study:

  • To investigate the role of advanced glycation endproducts (AGEs) and their receptor (RAGE) in diabetic atherosclerosis.
  • To establish and utilize a mouse model for accelerated diabetic atherosclerosis.
  • To evaluate the therapeutic potential of targeting the AGE-RAGE interaction.

Main Methods:

  • Development of a mouse model with accelerated atherosclerosis using apolipoprotein E deficiency in diabetic conditions.
  • Administration of the soluble extracellular domain of the receptor for advanced glycation endproducts (sRAGE) to diabetic mice.
  • Assessment of atherosclerosis progression and its dependence on glycemia and lipid levels.

Main Results:

  • Treatment with sRAGE completely suppressed accelerated atherosclerosis in diabetic apolipoprotein E-deficient mice.
  • The suppressive effect of sRAGE was independent of blood glucose and lipid levels.
  • This indicates a critical role for the AGE-RAGE axis in the pathogenesis of diabetic atherosclerosis.

Conclusions:

  • The interaction between advanced glycation endproducts and their receptor is a key driver of accelerated atherosclerosis in diabetes.
  • Targeting the AGE-RAGE pathway offers a promising therapeutic strategy for diabetic macrovascular disease.
  • This approach is effective irrespective of glycemic control or lipid profiles.

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