☆ 4.6 Review

Current progress of ferroptosis in cardiovascular diseases

FRONTIERS IN CARDIOVASCULAR MEDICINE (2023)

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ICA69 aggravates ferroptosis causing septic cardiac dysfunction via STING trafficking

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Hypoxia-elicited cardiac microvascular endothelial cell-derived exosomal miR-210-3p alleviate hypoxia/reoxygenation-induced myocardial cell injury through inhibiting transferrin receptor 1-mediated ferroptosis

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Counteraction of Myocardial Ferritin Heavy Chain Deficiency by Heme Oxygenase-1

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Ethoxyquin is a Competent Radical-Trapping Antioxidant for Preventing Ferroptosis in Doxorubicin Cardiotoxicity

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A non-canonical vitamin K cycle is a potent ferroptosis suppressor

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NATURE (2022)

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Iron Overload via Heme Degradation in the Endoplasmic Reticulum Triggers Ferroptosis in Myocardial Ischemia-Reperfusion Injury

Hiroko Deguchi Miyamoto et al.

Summary: This study demonstrates the significance of GPx4 regulation and iron overload-induced ferroptosis in ischemia-reperfusion injury. Ferroptosis is a major mode of cell death, distinct from mitochondrial permeability transition-driven necrosis. Therefore, targeting both modes may be an effective strategy to reduce infarct size and improve cardiac remodeling.

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Article Integrative & Complementary Medicine

Activation of p62-NRF2 Axis Protects against Doxorubicin-Induced Ferroptosis in Cardiomyocytes: A Novel Role and Molecular Mechanism of Resveratrol

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AMERICAN JOURNAL OF CHINESE MEDICINE (2022)

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Ablation of FUNDC1-dependent mitophagy renders myocardium resistant to paraquat-induced ferroptosis and contractile dysfunction

Hu Peng et al.

Summary: This study reveals that FUNDC1 plays a crucial role in paraquat-induced cardiac and mitochondrial injury. The loss of FUNDC1 can attenuate mitochondrial damage and cardiac dysfunction caused by paraquat. The mechanism underlying paraquat-induced cardiotoxicity involves ferroptosis mediated by FUNDC1 and JNK signaling pathway.

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE (2022)

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Article Biochemistry & Molecular Biology

Exosomal thioredoxin-1 from hypoxic human umbilical cord mesenchymal stem cells inhibits ferroptosis in doxorubicin-induced cardiotoxicity via mTORC1 signaling

Yue Yu et al.

Summary: This study compared the therapeutic effects of normoxic and hypoxic human umbilical cord mesenchymal stem cell-derived exosomes (Exo and Hypo-Exo) on doxorubicin (DOX)-induced ferroptosis and explored the underlying mechanisms. The results showed that Hypo-Exo exhibited better suppression of DOX-induced ferroptosis by regulating the Trx1-mTORC1-GPX4 pathway. This study suggests that Hypo-Exo may be a potential strategy against ferroptosis in DOX-induced cardiotoxicity.

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Article Biochemistry & Molecular Biology

Disruption of histamine/H1R-STAT3-SLC7A11 axis exacerbates doxorubicin-induced cardiac ferroptosis

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Summary: This study reveals the role of the histamine/H1R signaling pathway in doxorubicin-induced cardiotoxicity. Histamine deficiency or H1R antagonism accelerates myocardial ferroptosis and aggravates doxorubicin-induced cardiotoxicity. These findings provide a potential target for the treatment of doxorubicin-induced cardiotoxicity.

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Canagliflozin mitigates ferroptosis and improves myocardial oxidative stress in mice with diabetic cardiomyopathy

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Summary: This study suggests that Canagliflozin may alleviate diabetic cardiomyopathy by inhibiting ferroptosis, showing potential benefits for improving cardiac function and reducing cardiac damage.

FRONTIERS IN ENDOCRINOLOGY (2022)

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Review Cell Biology

Molecular Mechanisms of Ferroptosis and Relevance to Cardiovascular Disease

Lai-Hua Xie et al.

Summary: Ferroptosis is a regulated non-apoptotic cell death characterized by iron-dependence and the accumulation of lipid peroxidation. Excessive iron promotes the generation of soluble and lipid ROS through an iron-dependent Fenton reaction and lipoxygenase (LOX) enzyme activity, inducing ferroptosis. Cytosolic glutathione peroxidase 4 (cGPX4) and mitochondrial glutathione peroxidase 4 (mGPX4) serve as defense systems to detoxify lipid peroxidation in the cytoplasmic and mitochondrial membrane, respectively, defending against ferroptosis under normal conditions.

CELLS (2022)

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Article Cell Biology

TMEM43 Protects against Sepsis-Induced Cardiac Injury via Inhibiting Ferroptosis in Mice

Zhen Chen et al.

Summary: TMEM43 protects against sepsis-induced cardiac injury by inhibiting ferroptosis, suggesting it may be a potential therapeutic strategy for preventing sepsis.

CELLS (2022)

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Article Biology

IDH1 Promotes Foam Cell Formation by Aggravating Macrophage Ferroptosis

Ben Li et al.

Summary: In our study, we investigated the role of IDH1 in atherosclerotic foam cells. We found that inhibiting IDH1 can reduce macrophage ferroptosis and foam cell formation, which may provide insights into the occurrence and progression of atherosclerosis and potential treatment targets. The study also revealed the importance of ferroptosis and IDH1 in foam cell production.

BIOLOGY-BASEL (2022)

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Article Biochemistry & Molecular Biology

The SPATA2/CYLD pathway contributes to doxorubicin-induced cardiomyocyte ferroptosis via enhancing ferritinophagy

Yuan-Jing Zhou et al.

Summary: This study identifies a novel pathway, SPATA2/CYLD, which contributes to doxorubicin-induced cardiomyocyte ferroptosis by enhancing ferritinophagy through deubiquitination of NCOA4. Knockdown of SPATA2 attenuates cardiomyocyte injury and ferroptosis.

CHEMICO-BIOLOGICAL INTERACTIONS (2022)

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Article Pharmacology & Pharmacy

Ferroptosis occurs in phase of reperfusion but not ischemia in rat heart following ischemia or ischemia/reperfusion

Li-Jing Tang et al.

Summary: The study evaluated the contribution of ferroptosis to myocardial ischemia or reperfusion injury, finding that ferroptosis mainly occurs during myocardial reperfusion. The use of iron chelator deferoxamine attenuated reperfusion injury but had no significant effect on ischemic injury.

NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY (2021)

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Article Cardiac & Cardiovascular Systems

HSF1 functions as a key defender against palmitic acid-induced ferroptosis in cardiomyocytes

Nian Wang et al.

Summary: The study demonstrates that palmitic acid-induced cardiomyocyte death can be controlled by regulating the protein expression levels of HSF1 and GPX4, protecting cardiomyocytes from ferroptosis.

JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY (2021)

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Article Pharmacology & Pharmacy

Ferroportin-mediated ferroptosis involved in new-onset atrial fibrillation with LPS-induced endotoxemia

Jin Fang et al.

Summary: This study found significant activation of ferroptosis in a rat model of endotoxemia, as well as downregulation of ferroportin in the atrium, leading to increased vulnerability to AF. Inhibiting ferroptosis can alleviate AF vulnerability. The research reveals the important role of ferroportin-mediated ferroptosis in new-onset AF induced by sepsis.

EUROPEAN JOURNAL OF PHARMACOLOGY (2021)

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Review Cell Biology

Ferroptosis: mechanisms, biology and role in disease

Xuejun Jiang et al.

Summary: Ferroptosis, as a form of regulated cell death driven by iron-dependent phospholipid peroxidation, has seen significant growth in research in recent years. Studies have focused on molecular mechanisms, regulation, and functions of ferroptosis, linking this cell death modality to various pathologies and proposing its roles in normal physiology and potential therapeutic targeting.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2021)

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Article Cardiac & Cardiovascular Systems

MITOL/MARCH5 determines the susceptibility of cardiomyocytes to doxorubicin-induced ferroptosis by regulating GSH homeostasis

Hiroki Kitakata et al.

Summary: The study revealed that MITOL determines the fate of cardiomyocytes through the ferroptosis process and plays a key role in regulating vulnerability to DOX treatment.

JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY (2021)

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Article Endocrinology & Metabolism

Role of ferroptosis in the process of diabetes-induced endothelial dysfunction

Er-Fei Luo et al.

Summary: Ferroptosis is involved in endothelial dysfunction caused by diabetes, with activation of the p53-xCT-GSH axis playing a crucial role in endothelial cell ferroptosis and dysfunction.

WORLD JOURNAL OF DIABETES (2021)

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Article Biochemistry & Molecular Biology

ELAVL1 is transcriptionally activated by FOXC1 and promotes ferroptosis in myocardial ischemia/reperfusion injury by regulating autophagy

Hui-Yong Chen et al.

Summary: Myocardial ischemia is a common cardiovascular disease that can lead to significant morbidity and mortality. This study aimed to investigate the role of ELAVL1 in regulating myocardial ischemia and reperfusion injury, and found that ELAVL1 may promote ferroptosis through modulating autophagy, leading to myocardial injury. Inhibition of ELAVL1-mediated autophagic ferroptosis could be a potential new treatment strategy for myocardial I/R injury.

MOLECULAR MEDICINE (2021)

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Article Biotechnology & Applied Microbiology

Ferrostatin-1 alleviates lipopolysaccharide-induced cardiac dysfunction

Zheng Xiao et al.

Summary: This study demonstrates that Fer-1 can improve sepsis-induced cardiac dysfunction through multiple mechanisms, such as inhibiting ferroptosis, reducing cardiac damage and inflammatory responses.

BIOENGINEERED (2021)

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Article Biochemistry & Molecular Biology

Epigallocatechin-3-gallate pretreatment alleviates doxorubicin-induced ferroptosis and cardiotoxicity by upregulating AMPKα2 and activating adaptive autophagy

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Summary: The mechanism of Doxorubicin-induced cardiotoxicity is complex, involving multiple cell death forms, with clinical intervention effect not ideal. By inhibiting iron accumulation, oxidative stress, and abnormal lipid metabolism, it is possible to alleviate Doxorubicin-induced cardiotoxicity-induced ferroptosis and protect the myocardium. Epigallocatechin-3-gallate is a potential candidate phytochemical for combating Doxorubicin-induced cardiotoxicity.

REDOX BIOLOGY (2021)

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Article Pharmacology & Pharmacy

Ferroptosis is essential for diabetic cardiomyopathy and is prevented by sulforaphane via AMPK/NRF2 pathways

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Acta Pharmaceutica Sinica B (2021)

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Article Cardiac & Cardiovascular Systems

PDSS2 Inhibits the Ferroptosis of Vascular Endothelial Cells in Atherosclerosis by Activating Nrf2

Kai Yang et al.

Summary: PDSS2 may play a cardioprotective role in atherosclerosis (AS) by suppressing cell ferroptosis through activating the Nrf2 pathway, promoting proliferation of HCAECs.

JOURNAL OF CARDIOVASCULAR PHARMACOLOGY (2021)

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Review Immunology

Ferroptosis in infection, inflammation, and immunity

Xin Chen et al.

Summary: Ferroptosis is a form of regulated cell death triggered by iron toxicity, lipid peroxidation, and plasma membrane damage, and plays a role in shaping the immune response in health and disease.

JOURNAL OF EXPERIMENTAL MEDICINE (2021)

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Article Cardiac & Cardiovascular Systems

circSnx12 Is Involved in Ferroptosis During Heart Failure by Targeting miR-224-5p

Haoyuan Zheng et al.

Summary: This study investigated the regulatory mechanism of circRNA and iron metabolism in heart failure, identifying genes related to iron metabolism and constructing a circRNA-miRNA-mRNA regulatory network. Experimental validations in heart failure mice confirmed the predicted effects on FTH1 expression, as well as the presence of fibrosis and elevated levels of iron and MDA in myocardial tissues. The findings suggest potential circRNA targets for heart failure treatment.

FRONTIERS IN CARDIOVASCULAR MEDICINE (2021)

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Article Cardiac & Cardiovascular Systems

The SGLT-2 inhibitor empagliflozin improves myocardial strain, reduces cardiac fibrosis and pro-inflammatory cytokines in non-diabetic mice treated with doxorubicin

Vincenzo Quagliariello et al.

Summary: EMPA reduces ferroptosis, fibrosis, apoptosis, and inflammation in doxorubicin-treated non-diabetic mice through NLRP3 and MyD88-related pathways, resulting in significant improvements in cardiac functions. These findings provide a basis for translational studies aimed at reducing adverse cardiovascular outcomes in non-diabetic cancer patients treated with doxorubicin.

CARDIOVASCULAR DIABETOLOGY (2021)

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Review Cell Biology

Ferroptosis: the potential value target in atherosclerosis

Siyu Ouyang et al.

Summary: Cell death plays a crucial role in atherosclerosis, with ferroptosis accelerating endothelial dysfunction. Disordered intracellular iron damages various cell types and affects lipid peroxidation, oxidative stress, inflammation, and dyslipidemia in AS. The exact mechanisms through which ferroptosis initiates AS development and progression remain unclear.

CELL DEATH & DISEASE (2021)

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Review Cell Biology

Targeting Ferroptosis to Treat Cardiovascular Diseases: A New Continent to Be Explored

Fangze Huang et al.

Summary: Ferroptosis, a novel form of non-apoptotic regulated cell death driven by iron and lethal lipid hydroperoxides, plays a critical role in the development of cardiovascular diseases. Recent studies have shown that ferroptosis inhibitors and other substances can alleviate myocardial injury by targeting the ferroptosis pathway.

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2021)

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Review Oncology

Ferroptosis is a type of autophagy-dependent cell death

Borong Zhou et al.

SEMINARS IN CANCER BIOLOGY (2020)

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Article Biochemistry & Molecular Biology

ATF3 promotes erastin-induced ferroptosis by suppressing system Xc-

Liyuan Wang et al.

CELL DEATH AND DIFFERENTIATION (2020)

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Article Cardiac & Cardiovascular Systems

Loss of Cardiac Ferritin H Facilitates Cardiomyopathy via Slc7a11-Mediated Ferroptosis

Xuexian Fang et al.

CIRCULATION RESEARCH (2020)

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Article Cardiac & Cardiovascular Systems

Hypertension and Heart Failure Prevention, Targets, and Treatment

Katherine E. Di Palo et al.

HEART FAILURE CLINICS (2020)

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Article Chemistry, Multidisciplinary

GTP Cyclohydrolase 1/Tetrahydrobiopterin Counteract Ferroptosis through Lipid Remodeling

Vanessa A. N. Kraft et al.

ACS CENTRAL SCIENCE (2020)

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Article Oncology

Dexmedetomidine alleviated sepsis-induced myocardial ferroptosis and septic heart injury

Chunyan Wang et al.

MOLECULAR MEDICINE REPORTS (2020)

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Article Cardiac & Cardiovascular Systems

Molecular Basis of Atrial Fibrillation Pathophysiology and Therapy A Translational Perspective

Stanley Nattel et al.

CIRCULATION RESEARCH (2020)

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Article Biochemistry & Molecular Biology

Inhibition of ferroptosis alleviates atherosclerosis through attenuating lipid peroxidation and endothelial dysfunction in mouse aortic endothelial cell

Tao Bai et al.

FREE RADICAL BIOLOGY AND MEDICINE (2020)

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Article Cell Biology

Acyl-CoA thioesterase 1 prevents cardiomyocytes from Doxorubicin-induced ferroptosis via shaping the lipid composition

Yunchang Liu et al.

CELL DEATH & DISEASE (2020)

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Article Biochemistry & Molecular Biology

Ferritinophagy-mediated ferroptosis is involved in sepsis-induced cardiac injury

Ning Li et al.

FREE RADICAL BIOLOGY AND MEDICINE (2020)

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Article Cardiac & Cardiovascular Systems

2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines

Donna K. Arnett et al.

CIRCULATION (2019)

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Article Multidisciplinary Sciences

Ferroptosis as a target for protection against cardiomyopathy

Xuexian Fang et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2019)

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Article Cell Biology

ALOX12 is required for p53-mediated tumour suppression through a distinct ferroptosis pathway

Bo Chu et al.

NATURE CELL BIOLOGY (2019)

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Article Biochemistry & Molecular Biology

Role of TLR4/NADPH oxidase 4 pathway in promoting cell death through autophagy and ferroptosis during heart failure

Xiaoqing Chen et al.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2019)

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Review Physiology

FUNDAMENTAL MECHANISMS OF REGULATED CELL DEATH AND IMPLICATIONS FOR HEART DISEASE

Dominic P. Del Re et al.

PHYSIOLOGICAL REVIEWS (2019)

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Editorial Material Biochemistry & Molecular Biology

Iron and Atherosclerosis: The Link Revisited

Suowen Xu

TRENDS IN MOLECULAR MEDICINE (2019)

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Article Multidisciplinary Sciences

FSP1 is a glutathione-independent ferroptosis suppressor

Sebastian Doll et al.

NATURE (2019)

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Article Multidisciplinary Sciences

The CoQ oxidoreductase FSP1 acts parallel to GPX4 to inhibit ferroptosis

Kirill Bersuker et al.

NATURE (2019)

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Review Physiology

Mitochondrial Iron in Human Health and Disease

Diane M. Ward et al.

ANNUAL REVIEW OF PHYSIOLOGY, VOL 81 (2019)

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Article Hematology

Hepcidin Deficiency Protects Against Atherosclerosis

Rajeev Malhotra et al.

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY (2019)

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Review Cardiac & Cardiovascular Systems

From pediatrics to geriatrics: Mechanisms of heart failure across the life-course

Kathleen C. Woulfe et al.

JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY (2019)

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Review Biochemistry & Molecular Biology

NRF2 plays a critical role in mitigating lipid peroxidation and ferroptosis

Matthew Dodson et al.

REDOX BIOLOGY (2019)

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Review Oncology

The crosstalk between autophagy and ferroptosis: what can we learn to target drug resistance in cancer?

Yulu Zhou et al.

CANCER BIOLOGY & MEDICINE (2019)

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Article Cardiac & Cardiovascular Systems

Protective effects of the mechanistic target of rapamycin against excess iron and ferroptosis in cardiomyocytes

Yuichi Baba et al.

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY (2018)

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Article Cardiac & Cardiovascular Systems

Underestimated prevalence of heart failure in hospital inpatients: a comparison of ICD codes and discharge letter information

Mathias Kaspar et al.

CLINICAL RESEARCH IN CARDIOLOGY (2018)

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Article Biochemistry & Molecular Biology

FINO2 initiates ferroptosis through GPX4 inactivation and iron oxidation

Michael M. Gaschler et al.

NATURE CHEMICAL BIOLOGY (2018)

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Article Biochemistry & Molecular Biology

Unsolved mysteries: How does lipid peroxidation cause ferroptosis?

Huizhong Feng et al.

PLOS BIOLOGY (2018)

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Review Chemistry, Medicinal

The Role of NCOA4-Mediated Ferritinophagy in Health and Disease

Naiara Santana-Codina et al.

PHARMACEUTICALS (2018)

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Article Biochemistry & Molecular Biology

Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis

Valerian E. Kagan et al.

NATURE CHEMICAL BIOLOGY (2017)

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Article Biochemistry & Molecular Biology

ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition

Sebastian Doll et al.

NATURE CHEMICAL BIOLOGY (2017)

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Article Medicine, Research & Experimental

Iron accumulation, glutathione depletion, and lipid peroxidation must occur simultaneously during ferroptosis and are mutually amplifying events

Robert L. Bertrand

MEDICAL HYPOTHESES (2017)

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Article Oncology

Nrf2-Keap1 pathway promotes cell proliferation and diminishes ferroptosis

Z. Fan et al.

ONCOGENESIS (2017)

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Article Chemistry, Multidisciplinary

On the Mechanism of Cytoprotection by Ferrostatin-1 and Liproxstatin-1 and the Role of Lipid Peroxidation in Ferroptotic Cell Death

Omkar Zilka et al.

ACS CENTRAL SCIENCE (2017)

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A Red Carpet for Iron Metabolism

Martina U. Muckenthaler et al.

CELL (2017)

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Article Cell Biology

Autophagy promotes ferroptosis by degradation of ferritin

Wen Hou et al.

AUTOPHAGY (2016)

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Review Biochemistry & Molecular Biology

Ferroptosis: process and function

Y. Xie et al.

CELL DEATH AND DIFFERENTIATION (2016)

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Article Cardiac & Cardiovascular Systems

Endothelial Cell Dysfunction and the Pathobiology of Atherosclerosis

Michael A. Gimbrone et al.

CIRCULATION RESEARCH (2016)

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Editorial Material Cardiac & Cardiovascular Systems

Prevention: some important steps forward, but many unmet needs in a world with cardiovascular disease as the leading cause of death

Thomas F. Luscher

EUROPEAN HEART JOURNAL (2016)

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Article Biochemistry & Molecular Biology

Global survey of cell death mechanisms reveals metabolic regulation of ferroptosis

Kenichi Shimada et al.

NATURE CHEMICAL BIOLOGY (2016)

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Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis

Wan Seok Yang et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2016)

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Article Biology

An essential cell-autonomous role for hepcidin in cardiac iron homeostasis

Samira Lakhal-Littleton et al.

ELIFE (2016)

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Article Biochemistry & Molecular Biology

Human Haploid Cell Genetics Reveals Roles for Lipid Metabolism Genes in Nonapoptotic Cell Death

Scott J. Dixon et al.

ACS CHEMICAL BIOLOGY (2015)

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Structural basis of Keap1 interactions with Nrf2

Peter Canning et al.

FREE RADICAL BIOLOGY AND MEDICINE (2015)

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Article Biochemistry & Molecular Biology

Glutaminolysis and Transferrin Regulate Ferroptosis

Minghui Gao et al.

MOLECULAR CELL (2015)

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Article Biochemistry & Molecular Biology

Regulation of Ferroptotic Cancer Cell Death by GPX4

Wan Seok Yang et al.

CELL (2014)

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Article Biology

Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis

Scott J. Dixon et al.

ELIFE (2014)

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The oxidative stress-inducible cystine/glutamate antiporter, system xc-: cystine supplier and beyond

Marcus Conrad et al.

AMINO ACIDS (2012)

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Article Biochemistry & Molecular Biology

Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death

Scott J. Dixon et al.

CELL (2012)

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Article Biochemistry & Molecular Biology

Long-chain acyl-CoA synthetase 4 modulates prostaglandin E2 release from human arterial smooth muscle cells

Deidre L. Golej et al.

JOURNAL OF LIPID RESEARCH (2011)

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Article Cell Biology

Glutathione peroxidase 4 senses and translates oxidative stress into 12/15-lipoxygenase dependent- and AIF-Mediated cell death

Alexander Seiler et al.

CELL METABOLISM (2008)

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Article Multidisciplinary Sciences

Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization

E Nemeth et al.

SCIENCE (2004)

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