ArticleThe Journal of experimental medicine2019
Midkine drives cardiac inflammation by promoting neutrophil trafficking and NETosis in myocarditis.
Article in The Journal of experimental medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed, 129 citations in OpenAlex.
- Beyond the Human Body: Models for Studying Neutrophil Biology.Immunology and cell biology · 2026Review
- Cerebral venous outflow disturbance exacerbates ischemic stroke via an endothelium-initiated inflammatory cascade: an integrated single-cell transcriptomic analysis.Fluids and barriers of the CNS · 2026Article
- Dynamic neutrophil lipidome remodeling during induction of NETosis.Science advances · 2026Article
- Targeting MDK alleviates bone loss via dual regulation of osteogenic differentiation and inflammatory cytokine expression.Genes & diseases · 2026Article
- Remote neuromuscular electrical stimulation upregulates MDK to enhance macrophage efferocytosisJournal of biomedical research · 2026Article
- Myocardial and Vascular Involvement in COVID-19 and Post-Vaccination States: Understanding Injury Pathways and Clinical Implications.Life (Basel, Switzerland) · 2026Review
- Article
- Neutrophil Extracellular Traps in Heart Failure: From Pathophysiological Mechanisms to Therapeutic Targets.Journal of inflammation research · 2026Review
- Inflammatory responses driven by neutrophil extracellular traps in cardiovascular diseases: molecular mechanisms, emerging biomarkers, and therapeutic targets.Frontiers in immunology · 2026Review
- Integrated pharmacology and experimental validation reveals potential multiple mechanisms of the neutrophil elastase inhibitor sivelestat in attenuating myocarditis.Frontiers in pharmacology · 2026Article
- Stress-Induced Activation of Prolactin-NR4A1-Midkine Axis Exacerbates Skin Inflammation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Short-term outcome and prognostic factors in acute fulminant myocarditis with acute kidney injury patients.Frontiers in medicine · 2026Article
- Article
- Midkine Deficiency Attenuates Lipopolysaccharide-Induced Pulmonary Inflammation.International journal of molecular sciences · 2025Article
- Neutrophil Extracellular Traps in Cardiovascular Diseases: Pathological Roles and Therapeutic Implications.Biomolecules · 2025Review
- Neutrophils in Myocarditis: A Focus on the Secretory and Phagocytotic Functions.Reviews in cardiovascular medicine · 2025Review
- Exploring neutrophil extracellular traps: mechanisms of immune regulation and future therapeutic potential.Experimental hematology & oncology · 2025Review
- Deep insight into cytokine storm: from pathogenesis to treatment.Signal transduction and targeted therapy · 2025Review
- Systemic rewiring of dendritic cells by melanoma-secreted midkine impairs immune surveillance and response to immune checkpoint blockade.Nature cancer · 2025Article
- Review
25 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 6 institutions in 3 countries.
Funding
Abstract
Heart failure due to dilated cardiomyopathy is frequently caused by myocarditis. However, the pathogenesis of myocarditis remains incompletely understood. Here, we report the presence of neutrophil extracellular traps (NETs) in cardiac tissue of patients and mice with myocarditis. Inhibition of NET formation in experimental autoimmune myocarditis (EAM) of mice substantially reduces inflammation in the acute phase of the disease. Targeting the cytokine midkine (MK), which mediates NET formation in vitro, not only attenuates NET formation in vivo and the infiltration of polymorphonuclear neutrophils (PMNs) but also reduces fibrosis and preserves systolic function during EAM. Low-density lipoprotein receptor-related protein 1 (LRP1) acts as the functionally relevant receptor for MK-induced PMN recruitment as well as NET formation. In summary, NETosis substantially contributes to the pathogenesis of myocarditis and drives cardiac inflammation, probably via MK, which promotes PMN trafficking and NETosis. Thus, MK as well as NETs may represent novel therapeutic targets for the treatment of cardiac inflammation.
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Registered trials
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