Advanced glycation end product induced endothelial dysfunction through ER stress: Unravelling the role of Paraoxonase 2

Abstract

Hyperglycemia accelerates the formation of advanced glycation end products (AGEs). AGEs are a heterogeneous group of compounds generated by non-enzymatic glycation of proteins or lipids with glucose through Amadori rearrangement and its accumulation increases with aging in diabetes. AGEs augments ROS generation, diminishes the antioxidant defense of the cells, decreases mitochondrial membrane potential, ATP production, and elevates the levels of mitochondrial fission protein (Drp1) and mitophagic proteins (Parkin and PTEN) leading to dysfunction of mitochondria. In this chapter, we have discussed how AGEs trigger the endoplasmic reticulum stress and inflammation and mediate endothelial dysfunction in diabetes and also have discussed the role played by endogenous Paraoxonase 2 (PON2) in mitigating endothelial dysfunction by inhibiting the adverse effects of AGE.