The mechanisms of endothelial dysfunction in response to sustained hyperglycemia include: 1) Increased oxidative stress and generation of superoxide radicals [27]: oxidative stress could activate several pathways including PKC, glycation of cellular DNA and other macromolecules, polyol, hexosamine and nuclear factor Kappa B pathways - all of which contribute to worsening of endothelial dysfunction in diabetes; 2) Defected VEGF signaling pathway [6]: diabetic endothelial dysfunction downgrades the VEGF signaling pathway. This evidence concerns the gene PRRT2 and endothelial dysfunction.