Figure 2.

Targeted pathways by sirtuins in cardiac fibroblasts, cardiac myocytes, and in the vascular system. Sirt1 and Sirt6 prevent fibrosis and fibroblast hypertrophy by repressing growth factors such as TGF-β and IGF1, as well as inflammatory cytokines like TNF-α [24, 25]. At the vascular level, Sirt1 activation induces vasodilatation and promotes cell survival via deacetylation of eNOS and p53. The activity of eNOS and p53 increases in a Sirt1-dependent manner [26], whereas Sirt6 inhibits VCAM and TNFS protecting against atherosclerosis [27]. Sirt1 in the cardiac myocyte promotes mitochondrial biogenesis and function mainly through the activation of PGC1-α and Sirt3 [28], which activates mitochondrial dehydrogenases, enzymes from the electron transport chain, and the synthase and represses cyclophilin D, protecting the cell from the opening of the mitochondrial permeability transition pore [29–38]. Nuclear sirtuins 1 and 6 prevent cardiac hypertrophy and inflammation through the inactivation of the NF-κB pathway [24, 25], as well as IGF-Akt by Sirtuin 6 [25]. Sirtuins 1 and 3 are also regulators of oxidative stress through the regulation of FoxOs, and both promote DNA repair through the activation of Ku70 [39–42].