ArticleProceedings of the National Academy of Sciences of the United States of America2012
Cardiomyocyte-specific IκB kinase (IKK)/NF-κB activation induces reversible inflammatory cardiomyopathy and heart failure.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers, 1 of them a synthesis that pooled it.
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Who cites it
100 citing papers in PubMed, 1 synthesis or guideline pooled it, 169 citations in OpenAlex.
- Protein biomarkers of cardiac remodeling and inflammation associated with HFpEF and incident events.Scientific reports · 2022Pooled it
- Cardiac unloading models for myocardial reverse remodeling.Basic research in cardiology · 2026Review
- Tanshinone IIA alleviates inflammation and apoptosis in myocardial ischemia-reperfusion injury by modulating the MALT1/NF-κB/NLRP3 signaling axis.Histology and histopathology · 2026Article
- Multicellular senescence programs in the aged heart.Journal of molecular and cellular cardiology plus · 2026Review
- Targeting the AMPK Pathway with Natural Products for Heart Failure: A Systematic Review of Preclinical Evidence.Biomedicines · 2026Review
- Plasma-Derived Extracellular Vesicles Inhibit Lipopolysaccharide-Induced Apoptosis and Oxidative Stress in Human AC16 Cardiomyocytes.Current issues in molecular biology · 2026Article
- Signaling pathways and potential therapeutic agents in trastuzumab-induced cardiotoxicity.Apoptosis : an international journal on programmed cell death · 2026Review
- When ISG15 is involved in inflammation.Frontiers in immunology · 2026Review
- Cardiomyocytes regulate Inflammation in the failing heart.American journal of physiology. Heart and circulatory physiology · 2025Article
- Multiple low-dose radiation ameliorates type-2 diabetes mellitus via gut microbiota modulation to activate TLR4/MyD88/NF-κB pathway.BMC endocrine disorders · 2025Article
- The Abl1 tyrosine kinase is a key player in doxorubicin-induced cardiomyopathy and its p53/p73 cell death mediated signaling differs in atrial and ventricular cardiomyocytes.Journal of translational medicine · 2024Article
- Circulating Proteome Analysis Identifies Reduced Inflammation After Initiation of Hemodynamic Support with Either Veno-Arterial Extracorporeal Membrane Oxygenation or Impella in Patients with Cardiogenic Shock.Journal of cardiovascular translational research · 2024Article
- Hypoxic Preconditioning Attenuates Neuroinflammation via Inhibiting NF-κB/NLRP3 Axis Mediated by p-MLKL after Transient Global Cerebral Ischemia.Molecular neurobiology · 2024Article
- Interferons and interferon-related pathways in heart disease.Frontiers in cardiovascular medicine · 2024Review
- Inhibition of galectin-3 post-infarction impedes progressive fibrosis by regulating inflammatory profibrotic cascades.Cardiovascular research · 2023Article
- Hallmarks of cardiovascular ageing.Nature reviews. Cardiology · 2023Review
- SGLT2 Inhibitors in Aging-Related Cardiovascular Disease: A Review of Potential Mechanisms.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2023Review
- Promising Therapeutic Treatments for Cardiac Fibrosis: Herbal Plants and Their Extracts.Cardiology and therapy · 2023Review
- RGS7 balances acetylation/de-acetylation of p65 to control chemotherapy-dependent cardiac inflammation.Cellular and molecular life sciences : CMLS · 2023Article
- Identification of biomarkers and immune infiltration in acute myocardial infarction and heart failure by integrated analysis.Bioscience reports · 2023Article
40 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inflammation is a major factor in heart disease. IκB kinase (IKK) and its downstream target NF-κB are regulators of inflammation and are activated in cardiac disorders, but their precise contributions and targets are unclear. We analyzed IKK/NF-κB function in the heart by a gain-of-function approach, generating an inducible transgenic mouse model with cardiomyocyte-specific expression of constitutively active IKK2. In adult animals, IKK2 activation led to inflammatory dilated cardiomyopathy and heart failure. Transgenic hearts showed infiltration with CD11b(+) cells, fibrosis, fetal reprogramming, and atrophy of myocytes with strong constitutively active IKK2 expression. Upon transgene inactivation, the disease was reversible even at an advanced stage. IKK-induced cardiomyopathy was dependent on NF-κB activation, as in vivo expression of IκBα superrepressor, an inhibitor of NF-κB, prevented the development of disease. Gene expression and proteomic analyses revealed enhanced expression of inflammatory cytokines, and an IFN type I signature with activation of the IFN-stimulated gene 15 (ISG15) pathway. In that respect, IKK-induced cardiomyopathy resembled Coxsackievirus-induced myocarditis, during which the NF-κB and ISG15 pathways were also activated. Vice versa, in cardiomyocytes lacking the regulatory subunit of IKK (IKKγ/NEMO), the induction of ISG15 was attenuated. We conclude that IKK/NF-κB activation in cardiomyocytes is sufficient to cause cardiomyopathy and heart failure by inducing an excessive inflammatory response and myocyte atrophy.
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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.