Table 2.
SIRT3 targets in aging-associated cardiac pathophysiology.
| Aging-associated phenotype | Model system | SIRT3 Molecular target | Downstream effect | References |
|---|---|---|---|---|
| Hypertrophy | Whole body SIRT3-KO mice | FOXO3a | Catalase activity (↑) MnSOD activity (↑) |
(38) |
| Pressure overload by abdominal aortic banding in Wild type mice | LKB1 | mtUPR response (↑); Fatty acid metabolism (↑); Ketone metabolism (↑) |
(60) | |
| Cardiac fibrosis | Rat neonatal cardiomyocytes; Whole body SIRT3-KO mice | H3K27 | FOS expression (↓); Inflammatory and fibrotic response (↓) |
(42) |
| HFD-fed whole body SIRT3-KO mice | Not known | ROS levels (↓), NFKb-MCP-1 activity (↓), Macrophage infiltration (↓), Cardiac fibrosis (↓) |
(61) | |
| AngII-treated whole body SIRT3-KO mice; SIRT3 transgenic mice | GSK3β | Phosphorylation and degradation of Smad 3 and β-catenin (↑), Cardiac fibrosis (↓) |
(62) | |
| Neonatal rat fibroblasts | Not known | PPARγ expression and activity (↑), β-catenin degradation (↑), Cardiac fibrosis (↓) |
(63) | |
| Fibroblasts from whole body SIRT3-KO mice | STAT3 | NFATc2 expression (↓), Cardiac fibrosis (↓) |
(64) | |
| Cardiomyocyte loss | SIRT3 overexpressing cardiomyocytes | OPA1 | L-OPA to S-OPA form conversion (↓), Apoptosis (↓) |
(44) |
| H9C2 cardiomyocyte overexpressing SIRT3 | Not known | H2O2 levels (↓), NFkB activity (↑), Bcl2/Bax ratio (↑), Apoptosis (↓) |
(65) | |
| SIRT3 overexpressing rat neonatal cardiomyocytes | Ku70 | Bax sequestration (↑), Apoptosis (↓) |
(26) | |
| Cardiac-specific SIRT3-KO mice | p53 | Parkin activity (↑), mitophagy (↑) |
(41) | |
| Neonatal mice cardiomyocytes | Not known | AMPK activity (↑), Mitochondrial biogenesis (↑) |
(66) | |
| Insulin resistance | HFD-fed whole-body SIRT3-KO mice; Human umbilical vein endothelial cells | Not known | mtROS production (↓), eNOS activity (↑), NO production (↑), Insulin sensitivity (↑) |
(67) |