SIRT1 overexpression was shown to inhibit this harmful increase in p66Shc levels in HUVECs as well as protection against high glucose–induced endothelial dysfunction indicated by the increase in manganese superoxide dismutase (MnSOD) and decrease in plasminogen activator inhibitor-1 (PAI-1) expression. This evidence concerns the gene SERPINE1 and endothelial dysfunction.