NFE2L2 and Hyperglycemia: In support of previous mentioned studies, hyperglycemia-mediated oxidative stress activates NRF2 and its target genes in coronary arterial endothelial cells, and HFD-induced vascular ROS and endothelial dysfunction are even more intense in Nfe2l2-KO mice, indicating that the activation of NRF2 pathways confers endothelial protection under obesity and diabetes conditions (reviewed in [16,105]).