ArticleAmerican journal of physiology. Heart and circulatory physiology2021
Myeloid interleukin-4 receptor α is essential in postmyocardial infarction healing by regulating inflammation and fibrotic remodeling.
Article in American journal of physiology. Heart and circulatory physiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Macrophage Membrane-Coated Nanocarriers in Myocardial Infarction: A Paradigm Shift in Targeted Cardiac Therapy.International journal of nanomedicine · 2025Review
- Repair of the Infarcted Heart: Cellular Effectors, Molecular Mechanisms and Therapeutic Opportunities.Circulation research · 2024Review
- Global IL4Rα blockade exacerbates heart failure after an ischemic event in mice and humans.American journal of physiology. Heart and circulatory physiology · 2024Observational
- Review
- Emerging Anti-Inflammatory COPD Treatments: Potential Cardiovascular Impacts.International journal of chronic obstructive pulmonary disease · 2024Review
- IL-4 and IL-13 induce equivalent expression of traditional M2 markers and modulation of reactive oxygen species in human macrophages.Scientific reports · 2023Article
- Comparative Analysis of Heart Regeneration: Searching for the Key to Heal the Heart-Part II: Molecular Mechanisms of Cardiac Regeneration.Journal of cardiovascular development and disease · 2023Review
- Post-myocardial infarction fibrosis: Pathophysiology, examination, and intervention.Frontiers in pharmacology · 2023Review
- Interleukin 4/13 signaling in cardiac regeneration and repair.American journal of physiology. Heart and circulatory physiology · 2022Review
- Macrophages in myocardial infarction.American journal of physiology. Cell physiology · 2022Review
- Fibrosis of the diabetic heart: Clinical significance, molecular mechanisms, and therapeutic opportunities.Advanced drug delivery reviews · 2021Review
- Inactivation of Interleukin-4 Receptor α Signaling in Myeloid Cells Protects Mice From Angiotensin II/High Salt-Induced Cardiovascular Dysfunction Through Suppression of Fibrotic Remodeling.Journal of the American Heart Association · 2021Article
- Hematogenous Macrophages: A New Therapeutic Target for Spinal Cord Injury.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
Abstract
Interleukin-4 receptor α (IL4Rα) signaling plays an important role in cardiac remodeling during myocardial infarction (MI). However, the target cell type(s) of IL4Rα signaling during this remodeling remains unclear. Here, we investigated the contribution of endogenous myeloid-specific IL4Rα signaling in cardiac remodeling post-MI. We established a murine myeloid-specific IL4Rα knockout (MyIL4RαKO) model with LysM promoter-driven Cre recombination. Macrophages from MyIL4RαKO mice showed significant downregulation of alternatively activated macrophage markers but an upregulation of classical activated macrophage markers both in vitro and in vivo, indicating the successful inactivation of IL4Rα signaling in macrophages. To examine the role of myeloid IL4Rα during MI, we subjected MyIL4RαKO and littermate floxed control (FC) mice to MI. We found that cardiac function was significantly impaired as a result of myeloid-specific IL4Rα deficiency. This deficiency resulted in a dysregulated inflammatory response consisting of decreased production of anti-inflammatory cytokines. Myeloid IL4Rα deficiency also led to reduced collagen 1 deposition and an imbalance of matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs), with upregulated MMPs and downregulated TIMPs, which resulted in insufficient fibrotic remodeling. In conclusion, this study identifies that myeloid-specific IL4Rα signaling regulates inflammation and fibrotic remodeling during MI. Therefore, myeloid-specific activation of IL4Rα signaling could offer protective benefits after MI.
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