Fig. 5

Graphical representation of the role of dh404 in limiting diabetes-associated endothelial dysfunction. Hyperglycemia increases ROS generation, lowers endothelial derived NO and upregulates inflammatory pathways, in particular leukocyte–endothelial interactions which are mediated by VCAM-1. Consequently there is a reduction in vascular function, a phenomenon described as diabetes-associated endothelial dysfunction. Dh404 is an Nrf2 activator, which disrupts the Nrf2/Keap-1 interaction, thereby allowing Nrf2 to translocate to the nucleus where it modulates antioxidant and pro-inflammatory gene expression. This study demonstrates that the Nrf2 activator, dh404, inhibits ROS production, lessens pro-inflammatory mediators and improves vascular function. In particular, we show that dh404 downregulates VCAM-1 which is associated with reduced leukocyte–endothelial interactions. Black arrows represent stimulation; red dotted lines represent inhibition