ArticleCardiovascular research2022
Extracellular histones are a target in myocardial ischaemia-reperfusion injury.
Article in Cardiovascular research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
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
39 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Clinical efficacy of sacubitril-valsartan combined with acute ST-segment elevation myocardial infarction after reperfusion: A systematic review and meta-analysis.Frontiers in cardiovascular medicine · 2022Pooled it
- Epigenetic Mechanisms in Sepsis-Induced Cardiomyopathy: From Pathophysiology to Therapeutic Targets.International journal of molecular sciences · 2026Review
- Review
- Emerging biomodels to understand the pathophysiology of sepsis and evaluate new therapeutic strategies targeting extracellular histones.Materials today. Bio · 2026Review
- Damage-Associated Molecular Patterns in Perioperative Anesthesia Care: A Clinical Perspective.Anesthesia research · 2026Article
- The Fatty Acid Transporter CD36 Mediates Uptake, Biodistribution, and Cardioprotection by Small Extracellular Vesicles From HEK293 Cells.Journal of extracellular vesicles · 2026Article
- Epigenetic Liquid Biopsy Marks Atrial Fibrillation: Evidence from the AF Big Picture Study.Epigenomes · 2026Article
- Novel Selective Cardiac Myosin-Targeted Inhibitors Alleviate Myocardial Ischaemia-Reperfusion Injury.Cardiovascular drugs and therapy · 2026Article
- Neutrophil-mediated myocardial ischemia-reperfusion injury: mechanisms and potential therapeutic targets.Frontiers in immunology · 2026Review
- High-mobility group box 1 protein, histone H3 and histone H4 are not associated with peripheral hypoperfusion in sepsis: a retrospective cohort study.Einstein (Sao Paulo, Brazil) · 2026Article
- Cardioprotective effects of the extracellular chaperone clusterin in acute myocardial infarction.European journal of clinical investigation · 2025Article
- Review
- NETosis in myocardial ischemia-reperfusion injury: From mechanisms to therapies (Review).Biomedical reports · 2025Review
- Toll-Like Receptor 4-Mediated Neuroinflammation: Updates on Pathological Roles and Therapeutic Strategies in Chronic Cerebral Hypoperfusion.Molecular neurobiology · 2025Review
- High-Dose Tranexamic Acid Enhances Circulating Neutrophil Extracellular Traps and Thrombus in Thrombosis Mouse Model.Biomedicines · 2025Article
- Advances in neutrophil extracellular traps and ferroptosis in sepsis-induced cardiomyopathy.Frontiers in immunology · 2025Review
- From stress signals to fertility challenges: the role of damage-associated molecular patterns in male reproduction.Frontiers in immunology · 2025Review
- Endothelial Dysfunction and Cardiovascular Disease: Hyperbaric Oxygen Therapy as an Emerging Therapeutic Modality?Journal of cardiovascular development and disease · 2024Review
- The Crucial Triad: Endothelial Glycocalyx, Oxidative Stress, and Inflammation in Cardiac Surgery-Exploring the Molecular Connections.International journal of molecular sciences · 2024Review
- SGLT1 contributes to glucose-mediated exacerbation of ischemia-reperfusion injury in ex vivo rat heart.Basic research in cardiology · 2024Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 5 countries.
Funding
Abstract
aimsAcute myocardial infarction causes lethal cardiomyocyte injury during ischaemia and reperfusion (I/R). Histones have been described as important Danger Associated Molecular Proteins (DAMPs) in sepsis. The objective of this study was to establish whether extracellular histone release contributes to myocardial infarction. METHODS AND
resultsIsolated, perfused rat hearts were subject to I/R. Nucleosomes and histone-H4 release was detected early during reperfusion. Sodium-β-O-Methyl cellobioside sulfate (mCBS), a newly developed histone-neutralizing compound, significantly reduced infarct size whilst also reducing the detectable levels of histones. Histones were directly toxic to primary adult rat cardiomyocytes in vitro. This was prevented by mCBS or HIPe, a recently described, histone-H4 neutralizing peptide, but not by an inhibitor of TLR4, a receptor previously reported to be involved in DAMP-mediated cytotoxicity. Furthermore, TLR4-reporter HEK293 cells revealed that cytotoxicity of histone H4 was independent of TLR4 and NF-κB. In an in vivo rat model of I/R, HIPe significantly reduced infarct size.
conclusionHistones released from the myocardium are cytotoxic to cardiomyocytes, via a TLR4-independent mechanism. The targeting of extracellular histones provides a novel opportunity to limit cardiomyocyte death during I/R injury of the myocardium.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.