ArticleNature medicine2018
A proteolytic fragment of histone deacetylase 4 protects the heart from failure by regulating the hexosamine biosynthetic pathway.
Article in Nature medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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Who cites it
76 citing papers in PubMed, 136 citations in OpenAlex.
- Targeting ROAM1 with UDP-GlcNAc nanosheets selective activates lysosomal AMPK to resolve metabolic dysfunction-associated steatotic liver disease.Bioactive materials · 2026Article
- The histone deacetylase family in health and disease.Signal transduction and targeted therapy · 2026Review
- HDAC inhibition via suberoylanilide hydroxamic acid ameliorates doxorubicin-induced cardiotoxicity.Nature communications · 2026Article
- O-GlcNAcylation as a Metabolic Integrator in Cardiovascular Physiology and Disease.International journal of molecular sciences · 2026Review
- Cardiac epigenome in heart development and disease.Nature reviews. Cardiology · 2026Review
- Metabo-epigenetic circuits of heart failure: chromatin-modifying enzymes as determinants of metabolic plasticity.EMBO molecular medicine · 2026Review
- Transcriptional signature of cardiac myocyte recovery in mice and human reveals persistent upregulation of epigenetic factors.Epigenetics · 2025Article
- Role of Histone Deacetylase and Inhibitors in Cardiovascular Diseases.Cell proliferation · 2025Review
- HDAC4 Promotes Neuroprotection of Retinal Ganglion Cells After Optic Nerve Injury.Investigative ophthalmology & visual science · 2025Article
- Histone deacetylase 4: A therapeutic target for cardiovascular diseases (Review).International journal of molecular medicine · 2025Review
- Renal-Cardiac Crosstalk in the Pathogenesis and Progression of Heart Failure.Circulation research · 2025Review
- Single-nucleus multi-omics implicates androgen receptor signaling in cardiomyocytes and NR4A1 regulation in fibroblasts during atrial fibrillation.Nature cardiovascular research · 2025Article
- Physical exercise and epigenetic modifications in skeletal muscle, brain, and heart.Epigenetics & chromatin · 2025Review
- Nuclear receptor 4A1 Regulates Mitochondrial Homeostasis in Cardiac Post-Ischemic Injury by Controlling Mitochondrial Fission 1 Protein-Mediated Fragmentation and Parkin-Dependent Mitophagy.International journal of biological sciences · 2025Article
- Targeting oxidative stress in diabetic retinopathy: mechanisms, pathology, and novel treatment approaches.Frontiers in immunology · 2025Review
- Cardioepigenetics in action: aerobic exercise-induced modulation of miRNAs, lncRNAs, and chromatin remodeling in cardiovascular disease.Frontiers in cardiovascular medicine · 2025Review
- The new perspective of cardiac exercise rehabilitation: based on integrative physiology.Frontiers in physiology · 2025Review
- Decoding cardiac metabolic reprogramming through single-cell multi-omics: from mechanisms to therapeutic applications.Frontiers in cell and developmental biology · 2025Review
- Epigenetics in Heart Failure.International journal of molecular sciences · 2024Review
- Epigenetic regulation of cardiovascular diseases induced by behavioral and environmental risk factors: Mechanistic, diagnostic, and therapeutic insights.FASEB bioAdvances · 2024Review
16 more citing papers are in PubMed but not listed here.
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Authors and funding
38 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The stress-responsive epigenetic repressor histone deacetylase 4 (HDAC4) regulates cardiac gene expression. Here we show that the levels of an N-terminal proteolytically derived fragment of HDAC4, termed HDAC4-NT, are lower in failing mouse hearts than in healthy control hearts. Virus-mediated transfer of the portion of the Hdac4 gene encoding HDAC4-NT into the mouse myocardium protected the heart from remodeling and failure; this was associated with decreased expression of Nr4a1, which encodes a nuclear orphan receptor, and decreased NR4A1-dependent activation of the hexosamine biosynthetic pathway (HBP). Conversely, exercise enhanced HDAC4-NT levels, and mice with a cardiomyocyte-specific deletion of Hdac4 show reduced exercise capacity, which was characterized by cardiac fatigue and increased expression of Nr4a1. Mechanistically, we found that NR4A1 negatively regulated contractile function in a manner that depended on the HBP and the calcium sensor STIM1. Our work describes a new regulatory axis in which epigenetic regulation of a metabolic pathway affects calcium handling. Activation of this axis during intermittent physiological stress promotes cardiac function, whereas its impairment in sustained pathological cardiac stress leads to heart failure.
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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.