FIG. 2.

SIRT1 and SIRT6 response to cellular redox status and oxidative stress. At vascular level, the physiological functions of SIRT1 and SIRT6 in the control of the cellular redox state are mediated by deacetylation of multiple targets, including histones, transcription factors (FOXO, NF-κB, p53, and Nrf2), and enzymes involved in the vascular protection. SIRT6, a highly specific histone type 3 (H3) deacetylase, targets acetylated Lys-9 (acH3K9), Lys-56 (acH3K56), and Lys-18 (acH3K18). However, oxidative stress associated with various vascular pathophysiological conditions impairs SIRT1 and SIRT6 activities on their specific targets (rectangle enclosed), resulting in a decreased vascular protection against oxidative stress. →, positive regulation; ˧, negative regulation. CAT, catalase, eNOS, endothelial nitric oxide synthase; FOXO, forkhead box O; GPx, glutathione peroxidase; iNOS, inducible nitric oxide synthase; MnSOD, manganese superoxide dismutase; NF-κB, nuclear factor-kappa B; Nrf2, nuclear factor erythroid 2-related factor 2; PCAF, p300/CBP-associated factor; PPAR-α, peroxisome proliferator-activated receptor coactivator 1-α; SIRT, sirtuins.