Advanced glycation endproducts in diabetes-related macrovascular complications: focus on methylglyoxal

HighlightsThe reactive dicarbonyl methylglyoxal (MGO) is the major precursor of endogenously formed advanced glycation endproducts (AGEs).MGO is an important factor contributing to endothelial dysfunction by inducing oxidative stress, inflammation, apoptosis, and endoplasmic reticulum stress.AGEs stimulate cholesterol accumulation in macrophages and phenotype switching of vascular smooth muscle cells (VSMCs) into macrophage-like cells, while the impact of MGO is less understood.AGEs and MGO can inhibit angiogenesis, but promote atherosclerosis-linked inflammation by inducing inflammatory polarization of macrophages and the induction of inflammatory pathways.AGEs promote calcification of VSMCs by increasing the expression of osteogenic proteins and transcription factors. The impact of MGO on calcification remains to be elucidated.AbstractDiabetes is associated with vascular injury and the onset of macrovascular complications. Advanced glycation endproducts (AGEs) and the AGE precursor methylglyoxal (MGO) have been identified as key players in establishing the relationship between diabetes and vascular injury. While most research has focused on the link between AGEs and vascular injury, less is known about the effects of MGO on vasculature. In this review, we focus on the mechanisms linking AGEs and MGO to the development of atherosclerosis. AGEs and MGO are involved in many stages of atherosclerosis progression. However, more research is needed to determine the exact mechanisms underlying these effects. Nevertheless, AGEs and MGO could represent valid therapeutic targets for the macrovascular complications of diabetes.