Table 1 Potential main stimuli and FOXO1 related genes involved in DCM

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]