SIRT1 and Hyperglycemia: Besides, hyperglycemia can cause DNA damage and activate p53 [25,26] by producing methylglyoxal, as well as decrease the expression of sirtuin 3 (SIRT3) [17] and sirtuin 1 (SIRT1) [27] in HUVECs and promote HUVEC senescence via AQR/PLAU-related pathways [18] (Figure 6).