ArticlePloS one2014
N-acetyl-heparin attenuates acute lung injury caused by acid aspiration mainly by antagonizing histones in mice.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 21 citations in OpenAlex.
- IRF1-mediated sensing of oxidized mitochondrial DNA drives macrophage PANoptosis in lung ischemia-reperfusion injury.Apoptosis : an international journal on programmed cell death · 2026Article
- Targeting neutrophil extracellular traps: an emerging strategy for improving the management of refractory asthma.Frontiers in medicine · 2026Article
- Inhalation of an RNA aptamer that selectively binds extracellular histones protects from acute lung injury.Molecular therapy. Nucleic acids · 2023Article
- New anti-angiogenic compound based on chemically modified heparin.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2022Article
- Circulating extracellular histones exacerbate acute lung injury by augmenting pulmonary endothelial dysfunction via TLR4-dependent mechanism.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Extracellular histones are a target in myocardial ischaemia-reperfusion injury.Cardiovascular research · 2022Article
- Extracellular DNA Traps: Origin, Function and Implications for Anti-Cancer Therapies.Frontiers in oncology · 2022Review
- Heparin and non-anticoagulant heparin attenuate histone-induced inflammatory responses in whole blood.PloS one · 2020Article
- Biology, role and therapeutic potential of circulating histones in acute inflammatory disorders.Journal of cellular and molecular medicine · 2018Review
- Heparin and Heparin-Derivatives in Post-Subarachnoid Hemorrhage Brain Injury: A Multimodal Therapy for a Multimodal Disease.Molecules (Basel, Switzerland) · 2017Review
- Bone-marrow-derived mesenchymal stem cells inhibit gastric aspiration lung injury and inflammation in rats.Journal of cellular and molecular medicine · 2016Article
- The Endothelial Glycocalyx: New Diagnostic and Therapeutic Approaches in Sepsis.BioMed research international · 2016Review
- Extracellular histones in lung dysfunction: a new biomarker and therapeutic target?Pulmonary circulationReview
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Acute lung injury (ALI) is the leading cause of death in intensive care units. Extracellular histones have recently been recognized to be pivotal inflammatory mediators. Heparin and its derivatives can bind histones through electrostatic interaction. The purpose of this study was to investigate 1) the role of extracellular histones in the pathogenesis of ALI caused by acid aspiration and 2) whether N-acetyl-heparin (NAH) provides more protection than heparin against histones at the high dose. ALI was induced in mice via intratracheal instillation of hydrochloric acid (HCl). Lethality rate, blood gas, myeloperoxidase (MPO) activity, lung edema and pathological changes were used to evaluate the degree of ALI. Heparin/NAH was administered intraperitoneally, twice a day, for 3 days or until death. Acid aspiration caused an obvious increase in extracellular histones. A significant correlation existed between the concentration of HCl aspirated and the circulating histones. Heparin/NAH (10 mg/kg) improved the lethality rate, blood gas, MPO activity, lung edema and pathological score. At a dose of 20 mg/kg, NAH still provided protection, however heparin tended to aggravate the injury due to hemorrhagic complications. The specific interaction between heparin and histones was verified by the binding assay. In summary, high levels of extracellular histones can be pathogenic in ALI caused by acid aspiration. By neutralizing extracellular histones, heparin/NAH can offer similar protection at the moderate doses. At the high dose, NAH provides better protection than heparin.
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