Advanced glycation end products and receptor-oxidative stress system in diabetic vascular complications.
Reducing sugars can react non-enzymatically with amino groups of protein to form Amadori products. These early glycation products undergo further complex reactions, such as rearrangement, dehydration, and condensation, to become irreversibly cross-linked, heterogeneous fluorescent derivatives, termed advanced glycation end products (AGEs). The formation and accumulation of AGEs have been known to progress at an accelerated rate in patients with diabetes mellitus, thus being involved in the development and progression of diabetic micro- and macroangiopathy. Indeed, there is accumulating evidence that an interaction between an AGE and its receptor (RAGE) generates oxidative stress and subsequently evokes vascular inflammation and thrombosis, thereby playing a central role in diabetic vascular complications. In this paper, we review the pathophysiological role of AGE-RAGE-oxidative stress system and its therapeutic interventions in diabetic micro- and macroangiopathy.
Yamagishi
Sho-ichi
S
Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan. shoichi@med.kurume-u.ac.jp
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D003925:Diabetic Angiopathies / Q000503:physiopathology* / Q000628:therapy; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D018384:Oxidative Stress; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*
D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic