ArticleJACC. Basic to translational science2022
Iron Overload via Heme Degradation in the Endoplasmic Reticulum Triggers Ferroptosis in Myocardial Ischemia-Reperfusion Injury.
Article in JACC. Basic to translational science, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 90 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
90 citing papers in PubMed, 1 synthesis or guideline pooled it, 128 citations in OpenAlex.
- Quercetin-associated cardioprotection in preclinical myocardial ischemia-reperfusion injury: a systematic review and meta-analysis.Frontiers in pharmacology · 2026Pooled it
- Ubiquitination-dependent regulation of ferroptosis in ischemic heart and brain.Redox biology · 2026Review
- Ferroptosis: Newly Emerged Regulator for Human Disease.MedComm · 2026Review
- Heme cascade-triggered nanovesicles for myocardial ischemic core delivery.Bioactive materials · 2026Article
- Acid ceramidase modulates the lipid profile and exacerbates sensitivity to ferroptosis in WI-38 replicative senescent cells.Cell death & disease · 2026Article
- Potential Relationship Between Ferroptosis and Pyroptosis in Myocardial Ischemia/Reperfusion Injury: Molecular Mechanisms and Therapeutic Targets.Reviews in cardiovascular medicine · 2026Review
- Temporal changes of oxidative stress and ferroptosis-associated biomarkers in STEMI patients undergoing primary PCI and their correlation with myocardial reperfusion injury.BMC cardiovascular disorders · 2026Article
- ALDH2 Mediated Ferroptosis Regulation in Ischemia-Reperfusion Injury.Journal of cellular and molecular medicine · 2026Review
- Review
- Iron Balance and Cardiovascular Health: The Double-Edged Role of Deficiency and Overload.Cardiovascular toxicology · 2026Review
- Time-Stable Ferroptosis-Related Candidate Genes in Myocardial Ischemia/Reperfusion Injury Identified by Multi-Time-Point Transcriptomic Analysis: Prioritization of NCF2 Through Public Datasets and AC16 Cell Validation.Journal of inflammation research · 2026Article
- Does exercise modulate ferroptosis-related cardiovascular injury? Mechanistic evidence and translational boundaries.Frontiers in physiology · 2026Review
- Article
- Ferroptosis in Cardiovascular Diseases and Ferroptosis-Related Intervention Approaches.Cardiovascular drugs and therapy · 2025Review
- Phase-dependent iron dysmetabolism in myocardial ischemia-reperfusion injury: From mechanisms to therapies.American heart journal plus : cardiology research and practice · 2025Review
- SOX4 Promotes Ferroptosis to Aggravate Myocardial Ischemia/Reperfusion Injury Through Elevating DAPK1 Expression.Cardiovascular toxicology · 2025Article
- Acid ceramidase modulates the lipid profile and exacerbates sensitivity to ferroptosis in senescent cells.Research square · 2025Article
- Ferroptosis in Human Diseases: Fundamental Roles and Emerging Therapeutic Perspectives.Antioxidants (Basel, Switzerland) · 2025Review
- Repurposing cephalosporins as excellent anticancer agents and chemosensitizers for inflammation-driven cancer therapy.Scientific reports · 2025Article
- Advancements in nanomedicine for modulating ischemic cardiomyopathy therapy.Materials today. Bio · 2025Review
30 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issuedErratum.2024
Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ischemia-reperfusion (I/R) injury is a promising therapeutic target to improve clinical outcomes after acute myocardial infarction. Ferroptosis, triggered by iron overload and excessive lipid peroxides, is reportedly involved in I/R injury. However, its significance and mechanistic basis remain unclear. Here, we show that glutathione peroxidase 4 (GPx4), a key endogenous suppressor of ferroptosis, determines the susceptibility to myocardial I/R injury. Importantly, ferroptosis is a major mode of cell death in I/R injury, distinct from mitochondrial permeability transition (MPT)-driven necrosis. This suggests that the use of therapeutics targeting both modes is an effective strategy to further reduce the infarct size and thereby ameliorate cardiac remodeling after I/R injury. Furthermore, we demonstrate that heme oxygenase 1 up-regulation in response to hypoxia and hypoxia/reoxygenation degrades heme and thereby induces iron overload and ferroptosis in the endoplasmic reticulum (ER) of cardiomyocytes. Collectively, ferroptosis triggered by GPx4 reduction and iron overload in the ER is distinct from MPT-driven necrosis in both in vivo phenotype and in vitro mechanism for I/R injury. The use of therapeutics targeting ferroptosis in conjunction with cyclosporine A can be a promising strategy for I/R injury.
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Registered trials
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