ArticleThe Journal of clinical investigation2019
Ferroptotic cell death and TLR4/Trif signaling initiate neutrophil recruitment after heart transplantation.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 286 papers.
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Who cites it
286 citing papers in PubMed, 491 citations in OpenAlex.
- Spinal neuronal TLR4-induced enhancement of nociceptive signals contributes to myocardial ischemia/reperfusion injury.Basic research in cardiology · 2026Article
- Fate-mapping infiltrating monocytes following experimental myocardial infarction reveals differentiation trajectories in the infarcted heart.The Journal of clinical investigation · 2026Article
- Mechanisms underlying propagation of ferroptotic cell death.Nature cell biology · 2026Review
- Brown Adipocyte Sheets Alleviate Myocardial Ischemia-Reperfusion Injury Through NRG4-ErbB4-Dependent Ferroptosis Inhibition.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Review
- Clinical implications of ferroptosis in critical illness: a narrative review.Journal of intensive care · 2026Review
- Metal-dependent regulated cell death: Molecular architecture and translational frontiers.iMeta · 2026Review
- Implications of ferritinophagy in cardiovascular diseases and its pharmacological modulation: underlying mechanisms and clinical translation strategies.Cellular & molecular biology letters · 2026Review
- Ferroptosis in cardiovascular diseases: molecular mechanisms and a novel therapeutic target.Molecular biomedicine · 2026Review
- Multi-omics mapping identifies CYBA-mediated mitochondrial dysfunction driving macrophage polarization and ferroptosis via Nrf2 pathway in atherosclerosis.APL bioengineering · 2026Article
- ALDH2/eIF3E Interaction Modulates Protein Translation Critical for Cardiomyocyte Ferroptosis in Acute Myocardial Ischemia Injury.Circulation · 2026Article
- DNA-damaging chemotherapy reshapes cardiac-resident macrophage composition and function.Science immunology · 2026Article
- Ferroptosis and Alzheimer's disease: unraveling the molecular mechanisms and therapeutic opportunities.Frontiers in cell and developmental biology · 2026Review
- The ferroptosis-ncRNA-exosome triad: key orchestrators in cancer immunopathogenesis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Natural products in treating sepsis-associated lung and liver injuries by mediating ferroptosis, current progress, and future perspective.Frontiers in pharmacology · 2026Review
- Metabolic-epigenetic axis in cardiovascular inflammatory injury: regulatory mechanisms and intervention strategies.Frontiers in cardiovascular medicine · 2026Review
- Regulatory complexity and therapeutic targeting of the necroptosis network.Frontiers in immunology · 2026Review
- The Regulatory Landscape of Ferroptosis and Iron Homeostasis: Pathophysiological Mechanisms and Therapeutic Horizons in Cardiovascular Disease.Drug design, development and therapy · 2026Review
- Emerging links between TLR4 signaling and ferroptosis in heart failure.Frontiers in pharmacology · 2026Review
- Multiomics Profiling Identifies Tlr4 as a Therapeutic Target of Necroptosis in Spinal Cord Injury.Mediators of inflammation · 2026Article
226 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
21 authors at 3 institutions in 3 countries.
Funding
Abstract
Non-apoptotic forms of cell death can trigger sterile inflammation through the release of danger-associated molecular patterns, which are recognized by innate immune receptors. However, despite years of investigation the mechanisms which initiate inflammatory responses after heart transplantation remain elusive. Here, we demonstrate that ferrostatin-1 (Fer-1), a specific inhibitor of ferroptosis, decreases the level of pro-ferroptotic hydroperoxy-arachidonoyl-phosphatidylethanolamine, reduces cardiomyocyte cell death and blocks neutrophil recruitment following heart transplantation. Inhibition of necroptosis had no effect on neutrophil trafficking in cardiac grafts. We extend these observations to a model of coronary artery ligation-induced myocardial ischemia reperfusion injury where inhibition of ferroptosis resulted in reduced infarct size, improved left ventricular systolic function, and reduced left ventricular remodeling. Using intravital imaging of cardiac transplants, we uncover that ferroptosis orchestrates neutrophil recruitment to injured myocardium by promoting adhesion of neutrophils to coronary vascular endothelial cells through a TLR4/TRIF/type I IFN signaling pathway. Thus, we have discovered that inflammatory responses after cardiac transplantation are initiated through ferroptotic cell death and TLR4/Trif-dependent signaling in graft endothelial cells. These findings provide a platform for the development of therapeutic strategies for heart transplant recipients and patients, who are vulnerable to ischemia reperfusion injury following restoration of coronary blood flow.
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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.