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Advanced glycation end products in diabetic patients with optimized glycaemic control and their effects on endothelial reactivity: possible implications in venous graft failure
Author(s) -
Chello Massimo,
Spadaccio Cristiano,
Lusini Mario,
Covino Elvio,
Blarzino Carla,
De Marco Federico,
Di Domenico Fabio,
Coccia Raffaella
Publication year - 2009
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.966
Subject(s) - glycation , western blot , advanced glycation end product , medicine , endothelial dysfunction , receptor , downregulation and upregulation , endothelium , peroxisome proliferator activated receptor , andrology , rage (emotion) , endothelial stem cell , endocrinology , immunology , chemistry , biology , in vitro , biochemistry , gene , neuroscience
Background Diabetic patients exhibit an increased risk of saphenous graft occlusion after coronary bypass. Advanced glycation end products (AGEs) are ubiquitous signalling proteins that are associated with vascular and neurological complication of diabetes. The aim of this study is to verify whether AGE levels may promote endothelial cell alterations responsible for vein graft failure. Methods Segments of saphenous vein were obtained from both normal people and diabetic patients (HbA 1c < 6.0%) at the time of coronary surgery. Cultured endothelial cells were incubated in the absence/presence of AGEs (2 and 20 µM), and mRNA and protein for both receptor of AGEs (RAGE) and peroxisome proliferator‐activated receptors‐γ (PPAR‐γ) were analysed by real‐time polymerised chain reaction (PCR) and Western blot analysis. In the same fashion, the cell release of reactive oxygen species (ROS) was estimated in the absence/presence of AGEs by spectrofluorimetric analysis. Finally, neutrophil‐endothelial adhesion was evaluated in saphenous vein segments with and without the addition of AGEs. Results AGEs activated in a dose‐dependent manner the expression of RAGE and inhibited PPAR‐γ expression in endothelial cells as testified by both reverse transcription‐PCR (RT‐PCR) and Western blot analysis. Stimulation of cultured endothelial cells with AGEs significantly enhanced intracellular ROS formation in a dose‐dependent manner. Finally, neutrophil‐endothelial adhesion was significantly increased after incubation of control veins with AGEs. Conclusions These findings indicate that even in diabetic patients with HbA 1c < 6.0%, elevated serum levels of AGE determine a sort of a pro‐thrombotic state, providing a common mechanism that could explain the increased rate of vein graft occlusion in this population. Copyright © 2009 John Wiley & Sons, Ltd.