HIF1A and Hyperglycemia: Prolonged exposure to hyperglycemia also impairs endothelial function by downregulating endothelial NOS expression (Connell et al., 2007), which inhibits HIF1α accumulation (Gao et al., 2014), and by increasing the production of ROS and reactive nitrogen species (RNS) (Sena et al., 2013), which promote HIF1α degradation by activating PHDs.