Protein glycation: a firm link to endothelial cell dysfunction.
The advanced glycation end products (AGEs) are a heterogeneous class of molecules, including the following main subgroups: bis(lysyl)imidazolium cross-links, hydroimidazolones, 3-deoxyglucosone derivatives, and monolysyl adducts. AGEs are increased in diabetes, renal failure, and aging. Microvascular lesions correlate with the accumulation of AGEs, as demonstrated in diabetic retinopathy or renal glomerulosclerosis. On endothelial cells, ligation of receptor for AGE (RAGE) by AGEs induces the expression of cell adhesion molecules, tissue factor, cytokines such as interleukin-6, and monocyte chemoattractant protein-1. A chief means by which AGEs via RAGE exert their effects is by generation of reactive oxygen species, at least in part via stimulation of NADPH oxidase. Diabetes-associated vascular dysfunction in vivo can be prevented by blockade of RAGE. Thus, agents that limit AGE formation, increase the catabolism of these species, or antagonize their binding to RAGE may provide new targets for vascular protection in diabetes.
University Lariboisiere-Saint Louis and Institut National de la Transfusion Sanguine, Paris, France.
Jean-Luc
JL
Wautier
Ann Marie
AM
Schmidt
D000375:Aging / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured / Q000378:metabolism; D048909:Diabetes Complications / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000209:etiology / Q000378:metabolism; D003930:Diabetic Retinopathy / Q000209:etiology / Q000378:metabolism; D042783:Endothelial Cells / Q000502:physiology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006442:Glycated Hemoglobin / Q000009:adverse effects; D017127:Glycation End Products, Advanced / Q000009:adverse effects*; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D007791:Lactoylglutathione Lyase / Q000378:metabolism; D015416:Maillard Reaction; D009389:Neovascularization, Pathologic; D009569:Nitric Oxide / Q000172:deficiency; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction; D014666:Vasomotor System / Q000503:physiopathology
D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced; D007791:Lactoylglutathione Lyase; D009569:Nitric Oxide; D017382:Reactive Oxygen Species; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic