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Advanced glycation end products in diabetic patients with optimized glycaemic control and their effects on

Massimo Chello1, Cristiano Spadaccio, Mario Lusini

  • 1Department of Cardiovascular Sciences, University Campus Bio Medico of Rome, Rome, Italy. m.chello@unicampus.it

Diabetes/Metabolism Research and Reviews
|May 1, 2009
PubMed
Abstract

Insights

Advanced glycation end products (AGEs) promote vein graft occlusion in diabetic patients by increasing endothelial cell dysfunction and neutrophil adhesion, even with controlled blood sugar. This highlights a pro-thrombotic state contributing to graft failure.

Area of Science:

  • Vascular Biology
  • Diabetic Complications
  • Cardiovascular Surgery

Background:

  • Diabetic patients have higher saphenous vein graft occlusion rates post-coronary bypass.
  • Advanced glycation end products (AGEs) are linked to diabetic vascular complications.
  • This study investigates AGEs' role in endothelial cell alterations leading to vein graft failure.

Purpose of the Study:

  • To determine if AGE levels promote endothelial cell changes responsible for vein graft failure.
  • To investigate the impact of AGEs on RAGE and PPAR-gamma expression in endothelial cells.
  • To assess AGEs' effect on reactive oxygen species (ROS) production and neutrophil-endothelial adhesion.

Main Methods:

  • Saphenous vein segments from diabetic and non-diabetic patients were analyzed.
  • Endothelial cells were treated with AGEs (2 and 20 microM).
  • Gene and protein expression (RAGE, PPAR-gamma), ROS production, and neutrophil adhesion were measured.

Main Results:

  • AGEs increased RAGE and decreased PPAR-gamma expression in endothelial cells.
  • AGEs dose-dependently enhanced intracellular ROS formation.
  • Neutrophil-endothelial adhesion significantly increased upon AGEs incubation.

Conclusions:

  • Elevated AGEs induce a pro-thrombotic state in endothelial cells, even in well-controlled diabetics (HbA1c < 6.0%).
  • This mechanism contributes to the increased vein graft occlusion observed in diabetic patients.
  • AGEs represent a potential therapeutic target to improve vein graft patency.

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