Table 1.
Potential main stimuli and FOXO1 related genes involved in DCM
| FOXO1 stimuli | FOXO1 targeted genes | Function | Reference |
|---|---|---|---|
| Insulin | ↓Phosphoenolpyruvate carboxykinase (PEPCK) ↑Glucose-6-phosphatase (G6Pase) ↓Apolipoprotein C-III (apoC-III) |
↓Gluconeogensis Promotes blood glucose homeostasis by ↑glucose production ↓Triglyceride levels |
[42–44] |
| The Peroxisome Proliferator Activated Receptor (PPAR) γ Coactivator 1-α (PGC-1α) | ↑Pyruvate dehydrogenase kinase 4 (PDK4) | ↑Gluconeogenesis | [45] |
| Fructose Fibrates |
↑apoC-III ↓apoC-III |
↑Triglyceride levels ↓Triglyceride levels |
[46] |
| High glucose | ↑Thioredoxin interacting protein (Txnip) ↑Inducible nitric oxide synthase (iNOS)/Nitric oxide (NO) ↓Kruppel-like factor 2 (KLF2) ↑B cell leukemia/lymphoma 2-associated death promoter (BAD) |
↑Endothelial oxidative stress ↑Atherosclerosis ↑Endothelial dysfunction (impairment of endothelium-dependent vasodilatation) ↑Cell death |
[5, 47–49] |
| Vascular endothelial growth factor (VEGF) | ↑Manganese superoxide dismutase (MnSOD), ↑Bone morphogenic protein 2 (BMP2), ↑Vascular cell adhesion molecule (VCAM-1), ↑Matrix metalloproteinase-10 (MMP10) | ↑Endothelial cell survival and proliferation | [50] |
| Reactive oxygen species (ROS) | ↑iNOS/NO | ↓Endothelial function | [5] |
| Pressure overload, oxidative stress, sirtuin1 (SIRT1) | ↑Catalase | ↓Oxidative stress (Impaired ROS homeostasis) | [51] |
| Hydrogen peroxide (H2O2) | ↑Bim (Proapoptotic factor) | ↑Oxidative stress in endothelia cells | [52] |
| Tumor necrosis factor- α (TNF-α) | ↑CCAAT/enhancer binding protein (C/EBPβ) | ↑Production of proinflammatory cytokines like monocyte chemoattractant protein (MCP)-1, interleukin(IL)-6 | [53] |
| Insulin-like growth factor-1, angiotensin-II | ↑Modulatory calcineurin interacting protein exon 4 isoform (MCIP1.4) | ↑Cardiac hypertrophy | [54] |
| Poly(ADP-ribose)polymerase-1 (PARP-1) | ↓Cell cycle inhibitor p27(kip1) | ↑Cell proliferation | [55] |
| Endothelin-1 (ET-1) | ↓BAD | ↓Cell apoptosis | [49] |
| Resveratrol | ↑Rab7 | ↑Myocardial autophagic flux | [56] |
Different stimuli can activate or suppress FOXO1 signalling and several targeted genes may be controlled by FOXO1 in the diabetic conditions