ArticleCirculation. Arrhythmia and electrophysiology2019
HDAC (Histone Deacetylase) Inhibitor Valproic Acid Attenuates Atrial Remodeling and Delays the Onset of Atrial Fibrillation in Mice.
Article in Circulation. Arrhythmia and electrophysiology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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43 citing papers in PubMed, 71 citations in OpenAlex.
- Targeting the Epigenetic-Immune Axis in Acute Myeloid Leukemia: Current Advances and Future Directions.Current oncology reports · 2026Review
- Epigenetics in Atrial Fibrillation: Molecular Mechanisms and Therapeutic Avenues.Reviews in cardiovascular medicine · 2026Review
- Fto-mediated m6A demethylation of Lox drives atrial fibrosis and promotes atrial fibrillation in a murine model of hyperthyroidism.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2026Article
- Epigenetic Liquid Biopsy Marks Atrial Fibrillation: Evidence from the AF Big Picture Study.Epigenomes · 2026Article
- A modification of retrograde Langendorff-perfusion to increase the yield of CaFrontiers in pharmacology · 2026Article
- Molecular Mechanisms of Atrial Fibrillation Recurrence After Successful Catheter Ablation.Cells · 2025Review
- Role of Histone Deacetylase and Inhibitors in Cardiovascular Diseases.Cell proliferation · 2025Review
- Atrial cardiomyocyte-restricted cleavage of gasdermin D promotes atrial arrhythmogenesis.European heart journal · 2025Article
- Therapeutic potential and mechanistic insights of astragaloside IV in the treatment of arrhythmia: a comprehensive review.Frontiers in pharmacology · 2025Review
- Cardiac abnormalities and repolarization variability in epilepsy: influence of antiseizure medications and treatment response.Frontiers in cardiovascular medicine · 2025Article
- Aging-associated mechanisms of atrial fibrillation progression and their therapeutic potential.The journal of cardiovascular aging · 2024Article
- [Pathogenesis and potential diagnostic biomarkers of atrial fibrillation in Chinese population: a study based on bioinfor-matics].Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024Article
- Metabolic remodelling in atrial fibrillation: manifestations, mechanisms and clinical implications.Nature reviews. Cardiology · 2024Review
- Review
- Chromatin modifiers in human disease: from functional roles to regulatory mechanisms.Molecular biomedicine · 2024Review
- Epigenetics in diabetic cardiomyopathy.Clinical epigenetics · 2024Review
- Atrial fibrillation: pathophysiology, genetic and epigenetic mechanisms.The Lancet regional health. Europe · 2024Review
- Atrial Proteomic Profiling Reveals a Switch Towards Profibrotic Gene Expression Program in CREM-IbΔC-X Mice with Persistent Atrial Fibrillation.bioRxiv : the preprint server for biology · 2024Article
- Targeting histone deacetylase in cardiac diseases.Frontiers in physiology · 2024Review
- Traditional Therapeutics and Potential Epidrugs for CVD: Why Not Both?Life (Basel, Switzerland) · 2023Review
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundA structural, electrical and metabolic atrial remodeling is central in the development of atrial fibrillation (AF) contributing to its initiation and perpetuation. In the heart, HDACs (histone deacetylases) control remodeling associated processes like hypertrophy, fibrosis, and energy metabolism. Here, we analyzed, whether the HDAC class I/IIa inhibitor valproic acid (VPA) is able to attenuate atrial remodeling in CREM-IbΔC-X (cAMP responsive element modulator isoform IbΔC-X) transgenic mice, a mouse model of extensive atrial remodeling with age-dependent progression from spontaneous atrial ectopy to paroxysmal and finally long-lasting AF.
methodsVPA was administered for 7 or 25 weeks to transgenic and control mice. Atria were analyzed macroscopically and using widefield and electron microscopy. Action potentials were recorded from atrial cardiomyocytes using patch-clamp technique. ECG recordings documented the onset of AF. A proteome analysis with consecutive pathway mapping identified VPA-mediated proteomic changes and related pathways.
resultsVPA attenuated many components of atrial remodeling that are present in transgenic mice, animal AF models, and human AF. VPA significantly ( P<0.05) reduced atrial dilatation, cardiomyocyte enlargement, atrial fibrosis, and the disorganization of myocyte's ultrastructure. It significantly reduced the occurrence of atrial thrombi, reversed action potential alterations, and finally delayed the onset of AF by 4 to 8 weeks. Increased histone H4-acetylation in atria from VPA-treated transgenic mice verified effective in vivo HDAC inhibition. Cardiomyocyte-specific genetic inactivation of HDAC2 in transgenic mice attenuated the ultrastructural disorganization of myocytes comparable to VPA. Finally, VPA restrained dysregulation of proteins in transgenic mice that are involved in a multitude of AF relevant pathways like oxidative phosphorylation or RhoA (Ras homolog gene family, member A) signaling and disease functions like cardiac fibrosis and apoptosis of muscle cells.
conclusionsOur results suggest that VPA, clinically available, well-tolerated, and prescribed to many patients for years, has the therapeutic potential to delay the development of atrial remodeling and the onset of AF in patients at risk.
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