NOS3 and Hyperglycemia: As mentioned above, hyperglycemia induces oxidative stress, which may lead to endothelial dysfunction, mainly manifested in: Endothelial nitric oxide synthase (eNOS) activity is inhibited, NO synthesis is reduced, thrombosis factors (such as tissue factor and plasminogen activator inhibitors1) or ET-1 production is increased, which induces thrombosis and vasoconstriction, and nuclear factor kappaB (NF-κB) and activator protein1 are increased, leading to tissue inflammation (Defeudis et al. 2015).