Table 9 Epigenetic and posttranslational modification of ferroptosis in cardiovascular diseases
Diseases | Modification | Targets | Biological functions | Ref |
|---|---|---|---|---|
MIRI | ncRNA | NAMPT/Sirt1/FOX1/FTH1 | CircRNA FEACR alleviates MIRI through inhibiting ferroptosis by interacting with NAMPT, which increased NAMPT-dependent Sirtuin1 (Sirt1) expression, thereby promoting the transcriptional activity of FOXO1 by reducing FOXO1 acetylation levels, eventually upregulating the transcription of FTH1. | |
MIRI | ncRNA | SLC7A11 | Upregulated LncRNA SEMA5A-IT1 inhibits cardiomyocytes against hypoxia/reoxygenation injury partly through inhibiting ferroptosis via upregulating SLC7A11 by sponging miR-143-3p. | |
MIRI | ncRNA | TfR1 | miR-210-3p alleviate hypoxia/reoxygenation-induced myocardial cell injury through inhibiting ferroptosis via dowregulating TfR1. | |
MIRI | ncRNA | GLS2 | miR-190a-5p promotes ferroptosis through inhibiting GLS2. | |
MIRI | ncRNA | GPX4 | MiR-199a-5p promotes cardiomyocyte death in OGD/R-treated H9c2 cells through inducing ferroptosis via downregulation of GPX4 by inhibiting Akt/eNOS signaling pathway. | |
MIRI | ncRNA | ME2 | Upregulated miR-214-3p promotes MIRI through inducing ferroptosis via suppressing ME2. | |
MIRI | ncRNA | GPX4 | Egr-1-mediated upregulation of miR-15a-5p promotes MIRI through inducing ferroptosis via suppressing GPX4. | |
MIRI | Ubiquitination | Frataxin | Upregulated frataxin alleviates cardiomyocyte ferroptosis through upregulating FTH and downregulating TfR1. NHLRC1 mediates frataxin ubiquitination degradation. | |
MIRI | Ubiquitination | p53/TfR1 | USP7 promotes MIRI through inducing ferroptosis via activation of the p53/TfR1 pathway. | |
MIRI | Ubiquitination | SIRT1/p53/SLC7A11 | USP22 alleviates MIRI through inhibiting ferroptosis via the SIRT1-p53/SLC7A11. | |
Myocardial infarction | Phosphorylation | AKT/HIP-55 | Upregulated HIP-55 alleviates cardiomyocyte ferroptosis and MI injury.HIP-55 was identified as a new AKT substrate. AKT phosphorylates HIP-55 at S269/T291 sites and further HIP-55 directs AKT signaling to negatively regulate the MAP4K1 pathway against MI injury in a site-specific manner. S269A/T291A-mutated HIP-55 (HIP-55AA), which is defective in AKT phosphorylation and significantly decreases the interaction between HIP-55 and MAP4K1, failed to inhibit the MAP4K1/GPX4 ferroptosis. | |
DIC | m6A | TFRC | METTL14 promotes ferroptosis in doxorubicin-induced cardiomyocyte through stabilizing KCNQ1OT1 in a IGF2BP1 m6A manner to sponge miR-7-5p, thereby increasing levels of transferrin receptor. | |
DIC | Methylation | Nrf2/GPX4 | Upregulated PRMT4 aggravate DIC through promoting ferroptosis via interacting with Nrf2 to promote its enzymatic methylation, thereby suppressing GPX4. | |
DIC | Phosphorylation | AMPKα2 | Activation of AMPKα2 attenuated doxorubicin-induced cardiotoxicity through inhibiting ferroptosis. | |
DIC | Ubiquitination | Keap1 | TRIM21 ablation protects DIC through inhibiting ferroptosis via enhancing p62 sequestration of Keap1. | |
DIC | Ubiquitination | - | MITOL knockdown worsened vulnerability to DOX in cultured cardiomyocytes stressed with DOX. | |
DIC | Ubiquitination | NCOA4 | Upregulated SPATA2 recruit CYLD promotes ferritinophagy through decreasing NCOA4 ubiquitination and ferritin, and ferroptosis through increasing ACSL4. | |
Cardiac Fibrosis | Acetylation | p53 | Knockout of SIRT3 results in increased p53 acetylation and ferroptosis through downregulating GPX4 in the mouse hearts. SIRT3-mediated cardiac fibrosis was partly through a mechanism involving p53 acetylation-induced ferroptosis in myofibroblasts. | |
Cardiac Fibrosis | ncRNA | GPX4 | miR-375-3p promotes cardiac fibrosis through accelerating the ferroptosis of cardiomyocytes via downregulating GPX4. | |
Heart Failure | ncRNA | GPX4 | circSnx12 could act as an endogenous sponge to bind with miR-224-5p, and the 3’UTR region of FTH1 also had miRNA binding sites. | |
Heart Failure | Ubiquitination | Keap1/Nrf2 | Downregulated PGAM5 promotes ferroptosis in models of heart failure through decreasing Keap1 protein ubiquitination, thereby reducing activation of Nrf2. | |
HFD-induced cardiac injury | Phosphorylation | STAT3/NCOA4 | IL-6/STAT3 signaling promotes cardiac injury by upregulating NCOA4-mediated ferritinophagy and ferroptosis in high-fat-diet fed mice. | |
Cardiac Hypertrophy | Glycosylation | CD147 | CD147 promotes pathological cardiac remodeling and dysfunction through promoting ferroptosis in a glycosylation-dependent manner through binding the adaptor protein TRAF2 and activating the downstream TRAF2-TAK1 signaling pathway. | |
Aortic dissection | m6A | SLC7A11 | Upregulated METTL3 facilitates ferroptosis of HASMCs by promoting the mRNA degradation of SLC7A11 and FSP1. | |
SIC | - | SLC7A11/GPX4; P53 and ferritin | TMEM43 knockdown promotes LPS-induced mouse cardiac injury and dysfunction through inducing ferroptosis via upregulating the level of P53 and ferritin, while inhibiting the level of GPX4 and SLC7A11. |
