ArticleThe Journal of clinical investigation2021
Macrophage AXL receptor tyrosine kinase inflames the heart after reperfused myocardial infarction.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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The trial behind it
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Who cites it
63 citing papers in PubMed, 89 citations in OpenAlex.
- Timing-dependent anti-inflammatory effects of empagliflozin in monocyte-derived macrophages from post-myocardial infarct patients with type 2 diabetes.Cardiovascular diabetology · 2026Trial
- Radiation-induced AXL upregulation in CCR2Clinical and translational medicine · 2026Article
- Biomimetic nanodelivery of antagomiR-155-5p ameliorates wear particle-induced osteolysis by dual regulation of Gas6/Axl-mediated macrophage inflammation.Journal of orthopaedic translation · 2026Article
- Macrophage-induced immunomodulation in oral tissue repair and regeneration: Recent advances and future perspectives.Journal of advanced research · 2026Review
- Macrophage Efferocytosis in Heart.Arteriosclerosis, thrombosis, and vascular biology · 2026Review
- Spatiotemporally controlled restoration of GAS6 signaling via mRNA therapy promotes scarless healing in preclinical models.Nature communications · 2026Article
- Inactivation of AXL in Cardiac Fibroblasts Alleviates Right Ventricular Remodeling in Pulmonary Hypertension.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Discovery of novel biomarkers associated with myocardial fibrosis in chimpanzees (Frontiers in veterinary science · 2026Article
- Pregnancy-associated metabolic adaptations in circulating monocytes and macrophages favor clearance functions.Frontiers in immunology · 2026Article
- Efferocytosis in Health and Disease.MedComm · 2025Review
- Review
- Inhibition of Axl attenuates acute kidney injury by alleviating inflammation via SOCS3 downregulation in tubular epithelial cells.BMC nephrology · 2025Article
- Targeting the AXL pathway: a promising strategy for pulmonary fibrosis.The European respiratory journal · 2025Article
- Temporal single-cell sequencing analysis reveals that GPNMB-expressing macrophages potentiate muscle regeneration.Experimental & molecular medicine · 2025Article
- Staphylococcus aureus vesicles impair cutaneous wound healing through p38 MAPK-MerTK cleavage-mediated inhibition of macrophage efferocytosis.Cell communication and signaling : CCS · 2025Article
- Orderly Regulation of Macrophages and Fibroblasts by Axl in Bleomycin-Induced Pulmonary Fibrosis in Mice.Journal of cellular and molecular medicine · 2025Article
- STAMBPL1/TRIM21 Balances AXL Stability Impacting Mesenchymal Phenotype and Immune Response in KIRC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- METTL3, m6A modification, and EGR1: interplay affecting myocardial I/R injury outcomes.Cell biology and toxicology · 2024Article
- Phosphatidylserine externalization as immune checkpoint in cancer.Pflugers Archiv : European journal of physiology · 2024Review
- Functions of TAM Receptors and Ligands Protein S and Gas6 in Atherosclerosis and Cardiovascular Disease.International journal of molecular sciences · 2024Review
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
Tyro3, AXL, and MerTK (TAM) receptors are activated in macrophages in response to tissue injury and as such have been proposed as therapeutic targets to promote inflammation resolution during sterile wound healing, including myocardial infarction. Although the role of MerTK in cardioprotection is well characterized, the unique role of the other structurally similar TAMs, and particularly AXL, in clinically relevant models of myocardial ischemia/reperfusion infarction (IRI) is comparatively unknown. Utilizing complementary approaches, validated by flow cytometric analysis of human and murine macrophage subsets and conditional genetic loss and gain of function, we uncover a maladaptive role for myeloid AXL during IRI in the heart. Cross signaling between AXL and TLR4 in cardiac macrophages directed a switch to glycolytic metabolism and secretion of proinflammatory IL-1β, leading to increased intramyocardial inflammation, adverse ventricular remodeling, and impaired contractile function. AXL functioned independently of cardioprotective MerTK to reduce the efficacy of cardiac repair, but like MerTK, was proteolytically cleaved. Administration of a selective small molecule AXL inhibitor alone improved cardiac healing, which was further enhanced in combination with blockade of MerTK cleavage. These data support further exploration of macrophage TAM receptors as therapeutic targets for myocardial infarction.
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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.