Table 1.
FOXO3 cellular signaling in vascular aging-related diseases.
| Diseases | Biological effects of FOXO3 | References |
|---|---|---|
| Atherosclerosis | The longevity-associated G allele of FOXO3 SNP rs2802292 is protective against CAD mortality | (117) |
| Phosphorylated FOXO3 is increased in human carotid atherosclerotic plaques | (114) | |
| FOXO3 phosphorylated by Akt protects VSMCs from oxidative stress-induced apoptosis | (90) | |
| FOXO3 phosphorylation promotes VSMC migration | (114) | |
| Up-regulated AMPK/SIRT1/FOXO3 signaling increases the protein levels of the VSMC contractile markers | (84) | |
| FOXO3 suppresses VSMC proliferation and neointimal hyperplasia by downregulating CYR6 | (122) | |
| Decreased FOXO3 inhibits NLRP3-mediated EC pyroptosis | (123) | |
| Melatonin ameliorates atherosclerosis by regulating SIRT3/FOXO3/Parkin signaling | (124) | |
| Vascular calcification | FOXO3 phosphorylated by Akt promotes VSMC calcification | (125) |
| Vascular aging related-heart diseases | FOXO3-null mice developed dilated cardiomyopathy within 12 weeks of age | (129) |
| Reduced FOXO3 in senescent cardiac microvascular ECs leads to inhibition of proliferation and tube formation | (130) | |
| FOXO3 overexpression suppressed the aging of cardiac microvascular ECs by regulating the antioxidant/ROS/p27 (kip1) pathway | (130) | |
| Downstream proapoptotic genes mediated by FOXO3 are activated in aging cardiomyocytes | (133) | |
| FOXO3 deficiency in the heart enhances paraquat-induced aging phenotypes | (134) | |
| FOXO3 activation and expression are reduced in cardiac fibroblasts. Overexpression of FOXO3 inhibited while knockdown of FOXO3 enhanced TFGβ1-induced cardiac myofibroblasts transformation | (135) | |
| Vascular aging related-kidney diseases | FOXO3 promotes the expression of Atg proteins to sustain autophagy in the chronically hypoxic kidney | (101) |
| FOXO3 deacetylated by SIRT1 induces the expression of BNIP3, and ultimately promotes mitochondrial autophagy, and protect aging kidneys | (137) | |
| Tubular deletion of FOXO3 aggravates renal structural and functional damage | (138) | |
| Activated FOXO3 in mice with unilateral ureteral obstruction contributes to high levels of autophagy | (139) | |
| FOXO3 ameliorates oxidative stress, suppressing renal fibrosis induced by diabetes and hypertension | (141–143) | |
| Vascular aging related-cerebrovascular diseases | Increased risks of stroke are observed for FOXO3 block-A haplotype 2 “GAGC” and haplotype 4 “AAAT” carriers | (144) |
| Overexpressed FOXO3 in the cerebral cortex of MCAO mice promotes neuronal death | (145, 146) | |
| AMPK/FOXO3 and PTEN-Akt-FOXO3 pathways regulate neuronal apoptosis after hypoxia-ischemia in the developing rat brain | (67, 147) | |
| Increased FOXO3 activation has a protective effect on cerebral ischemia-reperfusion injury by promoting autophagy | (148) | |
| Primary hypertension | Longevity related FOXO3 variants may contribute to low risk for essential hypertension in Japanese women | (150) |