ArticleThe Journal of clinical investigation2024
NFĸB signaling drives myocardial injury via CCR2+ macrophages in a preclinical model of arrhythmogenic cardiomyopathy.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 22 citations in OpenAlex.
- Epicardial Contributions to Fibro-Inflammatory Signaling in a Pkp2-Deficient Arrhythmogenic Cardiomyopathy Model.Circulation. Heart failure · 2026Article
- Interleukin-1β Drives Disease Progression in Arrhythmogenic Cardiomyopathy.JACC. Basic to translational science · 2026Article
- Cardiac fibroblasts in myocardial injury and heart failure.European heart journal · 2026Review
- Cardiomyocyte-Specific Plakophilin-2 Loss Is Sufficient to Induce Aging and Senescence of Nonmyocytes: Relevance to Arrhythmogenic Cardiomyopathy.Journal of the American Heart Association · 2026Article
- Disruption of the Fibroinflammatory Loop: A Therapeutic Strategy for Cardiac Fibrosis in Non-Ischemic Cardiomyopathy.Reviews in cardiovascular medicine · 2026Article
- The role of macrophages in cardiac diseases: a review of the origins, functional diversity, and therapeutic potential.Frontiers in immunology · 2026Review
- Acute binge alcohol increases risk of arrhythmias and myocardial fibrosis in a mouse model of arrhythmogenic cardiomyopathy.American journal of physiology. Heart and circulatory physiology · 2025Article
- Cystathionine γ lyase deletion enhances corpus cavernosum contraction via thromboxane AAmerican journal of physiology. Regulatory, integrative and comparative physiology · 2025Article
- Desmoglein-2 deficiency results in cardiac dysfunction by compromising both Z-disc- and intercalated disc-mediated mechanotransduction.bioRxiv : the preprint server for biology · 2025Article
- Aging and sinus node dysfunction: mechanisms and future directions.Clinical science (London, England : 1979) · 2025Review
- Dysfunctional cardiomyocyte signalling and heart disease.Current opinion in cell biology · 2025Review
- Computational Modeling of Effects ofCirculation. Arrhythmia and electrophysiology · 2025Article
- Plasma CCL3 predicts adverse heart failure outcomes in patients with arrhythmogenic cardiomyopathy.BMC medicine · 2025Article
- Single-cell transcriptomic analysis reveals the association of Ccl6+Ccr2+Arg1+ macrophages with renal interstitial fibrosis in AKI.PloS one · 2025Article
- Interleukin-1β Drives Disease Progression in Arrhythmogenic Cardiomyopathy.bioRxiv : the preprint server for biology · 2024Article
- Prognostic Value of Circulating Biomarkers of Fibrotic Remodeling in Arrhythmogenic Cardiomyopathy.Biomedicines · 2024Article
- Review
- Single-Cell RNA Sequencing and Combinatorial Approaches for Understanding Heart Biology and Disease.Biology · 2024Review
- High-Fat Diet Augments Myocardial Inflammation and Cardiac Dysfunction in Arrhythmogenic Cardiomyopathy.Nutrients · 2024Article
- Targeting arrhythmogenic macrophages: lessons learned from arrhythmogenic cardiomyopathy.The Journal of clinical investigation · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Nuclear factor κ-B (NFκB) is activated in iPSC-cardiac myocytes from patients with arrhythmogenic cardiomyopathy (ACM) under basal conditions, and inhibition of NFκB signaling prevents disease in Dsg2mut/mut mice, a robust mouse model of ACM. Here, we used genetic approaches and single-cell RNA-Seq to define the contributions of immune signaling in cardiac myocytes and macrophages in the natural progression of ACM using Dsg2mut/mut mice. We found that NFκB signaling in cardiac myocytes drives myocardial injury, contractile dysfunction, and arrhythmias in Dsg2mut/mut mice. NFκB signaling in cardiac myocytes mobilizes macrophages expressing C-C motif chemokine receptor-2 (CCR2+ cells) to affected areas within the heart, where they mediate myocardial injury and arrhythmias. Contractile dysfunction in Dsg2mut/mut mice is caused both by loss of heart muscle and negative inotropic effects of inflammation in viable muscle. Single nucleus RNA-Seq and cellular indexing of transcriptomes and epitomes (CITE-Seq) studies revealed marked proinflammatory changes in gene expression and the cellular landscape in hearts of Dsg2mut/mut mice involving cardiac myocytes, fibroblasts, and CCR2+ macrophages. Changes in gene expression in cardiac myocytes and fibroblasts in Dsg2mut/mut mice were dependent on CCR2+ macrophage recruitment to the heart. These results highlight complex mechanisms of immune injury and regulatory crosstalk between cardiac myocytes, inflammatory cells, and fibroblasts in the pathogenesis of ACM.
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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 Socratic graph.