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Targeting ferroptosis: a novel insight against myocardial infarction and ischemia–reperfusion injuries

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Abstract

Ferroptosis, a newly discovered form of regulated cell death dependent on iron and reactive oxygen species, is mainly characterized by mitochondrial shrinkage, increased density of bilayer membranes and the accumulation of lipid peroxidation, causing membrane lipid peroxidation and eventually cell death. Similar with the most forms of regulated cell death, ferroptosis also participated in the pathological metabolism of myocardial infarction and myocardial ischemia/reperfusion injuries, which are still the leading causes of death worldwide. Given the crucial roles ferroptosis played in cardiovascular diseases, such as myocardial infarction and myocardial ischemia/reperfusion injuries, it is considerable to delve into the molecular mechanisms of ferroptosis contributing to the progress of cardiovascular diseases, which might offer the potential role of ferroptosis as a targeted treatment for a wide range of cardiovascular diseases. This review systematically summarizes the process and regulatory metabolisms of ferroptosis, discusses the relationship between ferroptosis and myocardial infarction as well as myocardial ischemia/reperfusion injuries, which might potentially provide novel insights for the pathological metabolism and original ideas for the prevention as well as treatment targeting ferroptosis of cardiovascular diseases such as myocardial infarction and myocardial ischemia/reperfusion injuries.

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Data availability

All the data generated during this study are included in this article and are available upon reasonable request to the first author.

Abbreviations

RCD:

Regulated cell death

MI:

Myocardial infarction

MIRI:

Myocardial ischemia/reperfusion injuries

CVDs:

Cardiovascular diseases

HF:

Heart failure

ROS:

Reactive oxygen species

RSL3:

RAS-selective lethal compound 3

PUFAs:

Polyunsaturated fatty acids

MUFAs:

Monounsaturated fatty acids

ACSL4:

Acyl-CoA synthetase long-chain family member 4

LPCAT3:

Lysophosphatidyl choline acyltransferase 3

LOXs:

Lipoxygenases

Lip:

Labile iron pool

GPX4:

Glutathione peroxidase 4

DMT1:

Divalent metal transporter 1

AGPS:

Alkyl glycerol phosphate synthase

FAR1:

Fatty acyl-CoA reductase 1

GNPAT:

Glyceronephosphate O-acyltransferase

AGPAT3:

1-Acylglycerol-3-phosphate O-acyltransferase 3

ER:

Endoplasmic reticulum

PEDS1:

Plasmanylethanolamine desaturase 1

Fe2+ :

Ferrous iron

Fe3+ :

Ferric iron

TF:

Transferrin

TFR1:

Transferrin receptor 1

STEAP3:

Six-transmembrane epithelial antigens of the prostate 3

FPN1:

Feroportin-1

NCOA4:

Nuclear receptor coactivator 4

HO-1:

Heme oxygenase-1

CO:

Carbon monoxide

Nrf2:

Nuclear factor erythroid 2-related factor 2

KEAP1:

Kelch-like ECH-associated protein 1

ARE:

Antioxidant response element

FTL:

The light chain of ferritin

FTH1:

The heavy chain of ferritin

FPN:

Ferroportin

HSPs:

Heat shock proteins

TRIM21:

Tripartite motif containing 21

HSPB1:

Heat shock protein beta-1

IREB-2:

Iron-responsive element-binding protein-2

CP:

Ceruloplasmin

LTF:

Lactose transferrin

PROM2:

Prominin-2

ATP:

Adenosine triphosphate

ISCs:

Iron-sulfur clusters

OXPHOS:

Oxidative phosphorylation

NOX4:

NADPH oxidase 4

TCA:

Tricarboxylic acid

MMP:

Mitochondrial membrane potential

ETC:

Electron transfer chain

Fer-1:

Ferrostatin-1

SLC3A2:

Solute carrier family 3 member 2

SLC7A11:

Catalytic subunit solute carrier family 7 member 11

Se:

Selenium

Sec:

Selenocysteine

SAT1:

Spermidine/spermine N1-acetyltransferase 1

ALOX-15:

Arachidonate lipoxygenase 15

ATF3:

Activating transcription factor 3

MVA:

Mevalonate

IPP:

Isopentenyl pyrophosphate

FSP1:

Ferroptosis suppressor protein 1

CoQ10:

Coenzyme Q10

NADPH:

Nicotinamide adenine dinucleotide phosphate

AIFM2:

Apoptosis-inducing factor mitochondrial 2

ESCRT:

Endosomal sorting complexes required for transport

PPARα:

Peroxisome proliferator-activated receptor α

MEG3:

Maternally-expressed gene 3

miR-214:

MicroRNA-214

GCH1:

GTP cyclohydrolase-1

BH4/BH2:

Tetrahydrobiopterin/dihydrobiopterin

RTAs:

Radical-trapping antioxidants

ox-LDLs:

Oxidized low-density lipoproteins

BACH1:

BTB and CNC homology 1

HUCB-MSCs:

Human umbilical cord blood-derived MSC exosomes

MLK3:

Mixed lineage kinase 3

CABG:

Coronary artery bypass grafting

MDA:

Malondialdehyde

ERS:

Endoplasmic reticulum stress

LVEF:

Left ventricular ejection fraction

OxPCs:

Oxidized phosphatidylcholines

USP22:

Ubiquitin-specific peptidase 22

LAD:

Left anterior descending coronary artery

USP7:

Ubiquitin-specific protease 7

ELAVL1:

Embryonic lethal-abnormal vision like protein 1: FOXC1: Forkhead box protein C1

H/R:

Hypoxia and reoxygenation

ERS:

Endoplasmic reticulum stress

DXZ:

Dexrazoxane

Lip-1:

Liproxstatin-1

HO-1:

Heme oxygenase-1

C3G:

Cyanidin-3-glucoside

CAD:

Coronary artery disease

DAMPs:

Damage-associated molecular patterns

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Funding

This work was supported by the National Natural Science Foundation of China (Grant No. 81870265, 82171808) and the China Young and Middle-aged Clinical Research Foundation (Grant No. 2017CCA-VG045), Foundation,2017CCA-VG045,2017CCA-VG045,2017CCA-VG045,2017CCA-VG045,2017CCA-VG045,2017CCA-VG045,2017CCA-VG045.

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  1. Cardiovascular Center, Beijing Tongren Hospital, Capital Medical University, No. 1 Dongjiaomin Lane, Dongcheng District, Beijing, 100730, People’s Republic of China

    Xuejie Han, Jie Zhang, Jian Liu & Caixia Guo

  2. Department of Physiology and Pathophysiology, Capital Medical University, No. 10 You An Men Wai Xi Tou Tiao, Fengtai District, Beijing, 100069, People’s Republic of China

    Hongxia Wang & Xiangjun Zeng

  3. Department of Geriatrics, Beijing Tiantan Hospital, Capital Medical University, No. 119 South 4Th Ring West Road, Fengtai District, Beijing, 100070, People’s Republic of China

    Fenghe Du

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XJH: writing—original draft preparation. XJH, JZ, JL and XJ: writing—review and editing. CXG: supervision. HXW, FHD and CXG: project administration. All authors have read and agreed to the published version of the manuscript.

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Han, X., Zhang, J., Liu, J. et al. Targeting ferroptosis: a novel insight against myocardial infarction and ischemia–reperfusion injuries. Apoptosis 28, 108–123 (2023). https://doi.org/10.1007/s10495-022-01785-2

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