Receptor of Advanced Glycation End Products (RAGE) Positively Regulates CD36 Expression and Reactive Oxygen Species Production in Human Monocytes in Diabetes

Abstract

Advanced glycation end products (AGEs) engagement of a monocyte surface receptor (RAGE) induces atherosclerosis. AGEs also act as CD36 ligands. We studied reactive oxygen species (ROS) and CD36 expression after siRNA inhibition of RAGE expression in human monocytes. We isolated monocytes from: a) 10 type 2 diabetics, and b) 5 age- and sex-matched healthy individuals. CD36 expression and ROS production were evaluated before and after RAGE knockdown. After incubation of monocytes with AGE + bovine serum albumin (BSA), CD36 expression and intracellular ROS increased significantly in all groups. In RAGE-knockdown monocytes, AGE-induced CD36 expression and ROS generation were also significantly inhibited. Blocking RAGE expression using siRNA in human monocytes led to a significant inhibition of CD36 expression and ROS production, suggesting a positive interaction between RAGE, CD36 expression and ROS generation in monocytes.