Role of advanced glycation end products (AGEs) and oxidative stress in vascular complications in diabetes

Abstract

BackgroundA non-enzymatic reaction between reducing sugars and amino groups of proteins, lipids and nucleic acids contributes to the aging of macromolecules, whose process has been known to progress at an accelerated rate under hyperglycemic and/or oxidative stress conditions. Over a course of days to weeks, early glycation products undergo further reactions such as rearrangements and dehydration to become irreversibly cross-linked, fluorescent protein derivatives termed advanced glycation end products (AGEs). Scope of reviewIn this paper, we review the role of AGE–oxidative stress axis and its therapeutic interventions in vascular complications in diabetes. Major conclusionsAGEs elicit oxidative stress generation and subsequently cause inflammatory and thrombogenic reactions in various types of cells via interaction with a receptor for AGEs (RAGE), thereby being involved in vascular complications in diabetes. In addition, mitochondrial superoxide generation has been shown to play an important role in the formation and accumulation of AGEs under diabetic conditions. Further, we have recently found that a pathophysiological crosstalk between AGE–RAGE axis and renin–angiotensin system (RAS) could contribute to the progression of vascular damage in diabetes. General significanceThese observations suggest that inhibition of AGE–RAGE–oxidative stress axis or blockade of its interaction with RAS is a novel therapeutic strategy for preventing vascular complications in diabetes.