ArticleThe Journal of experimental medicine2021
PMN-derived netrin-1 attenuates cardiac ischemia-reperfusion injury via myeloid ADORA2B signaling.
Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 46 citations in OpenAlex.
- The role of hypoxia-inducible factors in myocardial ischaemia-reperfusion injury and cardioprotection.Nature reviews. Cardiology · 2026Review
- Netrin-1 Promotes Pancreatic Tumorigenesis and Innervation through NEO1.Cancer research · 2026Article
- Review
- Hypoxia, ROS, and HIF Signaling in I/R Injury: Implications and Future Prospects.Antioxidants (Basel, Switzerland) · 2026Review
- Pharmacological Therapies for Consequences of Perinatal Hypoxic-Ischemic Brain Injury: Where Are We Now?International journal of molecular sciences · 2025Review
- Article
- Multifaceted roles of neutrophils in cardiac disease.Journal of leukocyte biology · 2025Review
- APurinergic signalling · 2025Review
- Adenosine and adenosine receptors: a "double-edged sword" in cardiovascular system.Frontiers in pharmacology · 2025Review
- The Cardioprotective Role of Neutrophil-Specific STING in Myocardial Ischemia/Reperfusion Injury.bioRxiv : the preprint server for biology · 2024Article
- Netrin-1 as A neural guidance protein in development and reinnervation of the larynx.Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft · 2024Review
- Targeting hypoxia-inducible factors: therapeutic opportunities and challenges.Nature reviews. Drug discovery · 2024Review
- Interplay of hypoxia-inducible factors and oxygen therapy in cardiovascular medicine.Nature reviews. Cardiology · 2023Review
- Macrophage neogenin deficiency exacerbates myocardial remodeling and inflammation after acute myocardial infarction through JAK1-STAT1 signaling.Cellular and molecular life sciences : CMLS · 2023Article
- Probiotic-Derived Ecto-5'-Nucleotidase Produces Anti-Inflammatory Adenosine Metabolites in Treg-Deficient Scurfy Mice.Probiotics and antimicrobial proteins · 2023Article
- AiScience · 2023Article
- Targeting myocardial equilibrative nucleoside transporter ENT1 provides cardioprotection by enhancing myeloid Adora2b signaling.JCI insight · 2023Article
- The Intriguing Role of Hypoxia-Inducible Factor in Myocardial Ischemia and Reperfusion: A Comprehensive Review.Journal of cardiovascular development and disease · 2023Review
- Probiotic-derived ecto-5'-nucleotidase produces anti-inflammatory adenosine metabolites in Treg-deficient scurfy mice.Research square · 2023Article
- Oxygen-generating microparticles downregulate HIF-1α expression, increase cardiac contractility, and mitigate ischemic injury.Acta biomaterialia · 2023Article
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
Previous studies implicated the neuronal guidance molecule netrin-1 in attenuating myocardial ischemia-reperfusion injury. However, the tissue-specific sources and receptor signaling events remain elusive. Neutrophils are among the first cells responding to an ischemic insult and can be associated with tissue injury or rescue. We found netrin-1 levels were elevated in the blood of patients with myocardial infarction, as well as in mice exposed to myocardial ischemia-reperfusion. Selectively increased infarct sizes and troponin levels were found in Ntn1loxP/loxP Lyz2 Cre+ mice, but not in mice with conditional netrin-1 deletion in other tissue compartments. In vivo studies using neutrophil depletion identified neutrophils as the main source for elevated blood netrin-1 during myocardial injury. Finally, pharmacologic studies using treatment with recombinant netrin-1 revealed a functional role for purinergic signaling events through the myeloid adenosine A2b receptor in mediating netrin-1-elicited cardioprotection. These findings suggest an autocrine signaling loop with a functional role for neutrophil-derived netrin-1 in attenuating myocardial ischemia-reperfusion injury through myeloid adenosine A2b signaling.
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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.