Because uncontrolled inflammation, oxidative stress, and defective autophagy all concur in the pathogenesis of diabetic micro- and macrovascular complications (Schrijvers et al., 2011; Tabas et al., 2015), we hypothesize that targeting Nrf2 in the diabetic milieu could lead to a concerted upregulation of cytoprotective pathways in the vasculature to mitigate atherosclerosis progression. This evidence concerns the gene NFE2L2 and atherosclerosis.