Regulation of Sirtuin-Mediated Protein Deacetylation by Cardioprotective Phytochemicals

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].