ArticleScience translational medicine2018
Histone deacetylase activity governs diastolic dysfunction through a nongenomic mechanism.
Article in Science translational medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
110 citing papers in PubMed, 1 synthesis or guideline pooled it, 158 citations in OpenAlex.
- Effectiveness of various exercise interventions on peak VOBMC cardiovascular disorders · 2026Pooled it
- Diastolic contributors in cardiomyocytes of a cardiometabolic HFpEF-like mouse model.The Journal of general physiology · 2026Article
- Epigenetics in development, disease, and therapy: from mechanisms to clinical interventions.Science China. Life sciences · 2026Review
- Obstructive Sleep Apnea and Cardiovascular Disease: Mechanisms, Diagnostics, and Emerging Therapeutic Approaches.Biomedicines · 2026Review
- Molecular Mechanisms and Multi-Omics Integration in Heart Failure: From Pathophysiology to Precision Medicine.International journal of molecular sciences · 2026Review
- Integrated epigenetic networks in aging: from histone to RNA modifications.Journal of translational medicine · 2026Review
- Metabo-epigenetic circuits of heart failure: chromatin-modifying enzymes as determinants of metabolic plasticity.EMBO molecular medicine · 2026Review
- ABCC9 knockdown attenuates isoproterenol‑induced myocardial hypertrophy by inhibiting the PI3K/AKT signaling pathway.Molecular medicine reports · 2026Article
- Role of Histone Deacetylase and Inhibitors in Cardiovascular Diseases.Cell proliferation · 2025Review
- Epigenetic Regulation of Aging and its Rejuvenation.MedComm · 2025Review
- Anti-ageing interventions for the treatment of cardiovascular disease.Cardiovascular research · 2025Review
- Cellular and Molecular Mechanisms Explaining the Link Between Inflammatory Bowel Disease and Heart Failure.Cells · 2025Review
- Glycerol storage increases passive stiffness of muscle fibers through effects on titin extensibility.The Journal of general physiology · 2025Article
- Enzyme-independent functions of HDAC3 in the adult heart.Acta pharmaceutica Sinica. B · 2025Article
- Cardiac Fibrosis in the Multi-Omics Era: Implications for Heart Failure.Circulation research · 2025Review
- Role of Protein Lysine Acetylation in the Pathogenesis and Treatment of Obesity and Metabolic Syndrome.Current obesity reports · 2025Review
- Caloric restriction and its mimetics in heart failure with preserved ejection fraction: mechanisms and therapeutic potential.Cardiovascular diabetology · 2025Review
- Leveraging metabolism for better outcomes in heart failure.Cardiovascular research · 2024Review
- Exogenous Nucleotides Mitigate Cardiac Aging in SAMP8 Mice by Modulating Energy Metabolism Through AMPK Pathway.Nutrients · 2024Article
- Epigenetics in Heart Failure.International journal of molecular sciences · 2024Review
50 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
There are no approved drugs for the treatment of heart failure with preserved ejection fraction (HFpEF), which is characterized by left ventricular (LV) diastolic dysfunction. We demonstrate that ITF2357 (givinostat), a clinical-stage inhibitor of histone deacetylase (HDAC) catalytic activity, is efficacious in two distinct murine models of diastolic dysfunction with preserved EF. ITF2357 blocked LV diastolic dysfunction due to hypertension in Dahl salt-sensitive (DSS) rats and suppressed aging-induced diastolic dysfunction in normotensive mice. HDAC inhibitor-mediated efficacy was not due to lowering blood pressure or inhibiting cellular and molecular events commonly associated with diastolic dysfunction, including cardiac fibrosis, cardiac hypertrophy, or changes in cardiac titin and myosin isoform expression. Instead, ex vivo studies revealed impairment of cardiac myofibril relaxation as a previously unrecognized, myocyte-autonomous mechanism for diastolic dysfunction, which can be ameliorated by HDAC inhibition. Translating these findings to humans, cardiac myofibrils from patients with diastolic dysfunction and preserved EF also exhibited compromised relaxation. These data suggest that agents such as HDAC inhibitors, which potentiate cardiac myofibril relaxation, hold promise for the treatment of HFpEF in humans.
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What OpenQuestion holds
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 OpenQuestion graph.