ArticleBlood2014
VWF-mediated leukocyte recruitment with chromatin decondensation by PAD4 increases myocardial ischemia/reperfusion injury in mice.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 190 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
190 citing papers in PubMed, 1 synthesis or guideline pooled it, 271 citations in OpenAlex.
- Cardiac repair after myocardial infarction: A two-sided role of inflammation-mediated.Frontiers in cardiovascular medicine · 2022Pooled it
- Tocilizumab increases citrullinated histone 3 in non-ST segment elevation myocardial infarction.Open heart · 2021Trial
- Neutrophil extracellular trap components and myocardial recovery in post-ischemic acute heart failure.PloS one · 2020Trial
- Neutrophil extracellular trap formation and circulating nucleosomes in patients with chronic myeloproliferative neoplasms.Scientific reports · 2016Trial
- Review
- Review
- Spatiotemporal Nanotherapy After Myocardial Infarction: Targeting the Inflammatory-to-reparative Transition With Extracellular Vesicles and Engineered Nanoparticles.Cardiovascular drugs and therapy · 2026Review
- Toll-like receptor 7 constrains efferocytosis in myocardial injury.Basic research in cardiology · 2026Article
- Von Willebrand factor A2 domain inhibits A1-DNA binding while preserving A1-platelet interaction under flow: evidence from recombinant domain constructs.Research and practice in thrombosis and haemostasis · 2026Article
- ADAM and ADAMTS proteases as integrative hubs in heart failure pathogenesis and therapy.iScience · 2026Review
- Review
- Comprehensive Evaluation of YJ-2 as a PAD4 Inhibitor in Alleviating Ischemic Brain Injury: From NETs-Induced Neurotoxicity to In Vivo Neuroprotection.CNS neuroscience & therapeutics · 2026Article
- Mouse models to study von Willebrand factor in inflammation: a scoping review.Intensive care medicine experimental · 2026Review
- GPR30-mediated NETs degradation via Trex1 in heart failure of aged female mice.Journal of translational medicine · 2026Article
- Long-term social isolation during adolescence exacerbated cardiac dysfunction after myocardial infarction.Translational psychiatry · 2026Article
- Bioresorbable Vascular Stents: How Neutrophil Extracellular Traps Influence Biocompatibility, Degradation Kinetics, and Device Performance.Bioengineering (Basel, Switzerland) · 2026Review
- Immune and stromal remodeling underlies radiation-induced heart injury: insights from single-cell transcriptomics.Frontiers in cardiovascular medicine · 2026Article
- Review
- Citrullination Accompanies the Development of Carotid Atherosclerotic Plaques.Current medicinal chemistry · 2026Article
- Inflammatory responses driven by neutrophil extracellular traps in cardiovascular diseases: molecular mechanisms, emerging biomarkers, and therapeutic targets.Frontiers in immunology · 2026Review
130 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Innate immune cells play a major role in the early response to myocardial ischemia/reperfusion (MI/R) injury. Recombinant human ADAMTS13 (rhADAMTS13), cleaving von Willebrand factor (VWF), reduces leukocyte recruitment in mice. Death of cardiomyocytes and the possible formation of neutrophil extracellular traps (NETs) may result in chromatin release that is prothrombotic and cytotoxic. We investigated the pathophysiological role of extracellular chromatin during MI/R to evaluate the therapeutic potential of targeting extracellular DNA and VWF by using DNase I with/without rhADAMTS13. Finally, we examined the impact of histone citrullination and NETosis by peptidylarginine deiminase 4 (PAD4) on MI/R. We used a 24-hour MI/R mouse surgical model. MI/R injury caused an increase in plasma nucleosomes, abundant neutrophil infiltration, and the presence of citrullinated histone H3 at the site of injury. Both monotherapies and coadministration of DNase I and rhADAMTS13 revealed a cardioprotective effect, resulting in subsequent improvement of cardiac contractile function. PAD4(-/-) mice, which do not produce NETs, were also significantly protected from MI/R and DNase I treatment had no further beneficial effect. We demonstrate that extracellular chromatin released through NETosis exacerbates MI/R injury. Targeting both VWF-mediated leukocyte recruitment and chromatin removal may be a new therapeutic strategy to reduce ischemia-related cardiac damage.
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What OpenQuestion holds
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.