ArticleThe Journal of clinical investigation2022
HDAC6 modulates myofibril stiffness and diastolic function of the heart.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 49 citations in OpenAlex.
- Diastolic contributors in cardiomyocytes of a cardiometabolic HFpEF-like mouse model.The Journal of general physiology · 2026Article
- Transcriptome Reprogramming in Heart Failure: The Hidden Splicing Code.Current cardiology reports · 2026Review
- Titin's P-zone domains A164-167 are essential for thick filament structural arrangement.The Journal of general physiology · 2026Article
- Cardiometabolic adaptations in the cave nectar bat Eonycteris spelaea.Communications biology · 2026Article
- Targeting ADAMTS1/HDAC6 alleviates TGF-β1/SMAD2-associated cardiac fibrosis in cardiac fibrosis post-myocardial infarction.Cell biology and toxicology · 2026Article
- Multi-omics Insight into Cardiac Myofibril Remodeling in Post-Prandial Burmese Pythons.bioRxiv : the preprint server for biology · 2026Article
- Metabo-epigenetic circuits of heart failure: chromatin-modifying enzymes as determinants of metabolic plasticity.EMBO molecular medicine · 2026Review
- Role of Histone Deacetylase and Inhibitors in Cardiovascular Diseases.Cell proliferation · 2025Review
- Rbm20 antisense oligonucleotides alleviate diastolic dysfunction in a mouse model of cardiometabolic heart failure (HFpEF).Cardiovascular research · 2025Article
- What Is Cardiometabolic HFpEF and How Can We Study it Preclinically?JACC. Basic to translational science · 2025Review
- Low Dose GLP-1 Therapy Attenuates Pathological Cardiac and Hepatic Remodelling in HFpEF Independent of Weight Loss.bioRxiv : the preprint server for biology · 2025Article
- Novel Drug Targets in Diastolic Heart Disease.International journal of molecular sciences · 2025Review
- Glycerol storage increases passive stiffness of muscle fibers through effects on titin extensibility.The Journal of general physiology · 2025Article
- The role of HDAC6 in fibrosis: a novel and effective therapy strategy.European journal of medical research · 2025Review
- Myocardial transcriptomic and proteomic landscapes across the menopausal continuum in a murine model of chemically induced accelerated ovarian failure.Physiological genomics · 2025Article
- Histone Deacetylase 6 Controls Atrial Fibrosis and Remodeling in Postinfarction Mice Through the Modulation of Wnt3a/GSK-3β Signaling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Article
- Epigenetics in Heart Failure.International journal of molecular sciences · 2024Review
- Genetic deletion or pharmacologic inhibition of histone deacetylase 6 protects the heart against ischaemia/reperfusion injury by limiting tumour necrosis factor alpha-induced mitochondrial injury in experimental diabetes.Cardiovascular research · 2024Article
- Integrative proteomic and metabolomic elucidation of cardiomyopathy with in vivo and in vitro models and clinical samples.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
Corrections and comments
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Authors and funding
19 authors at 4 institutions in 3 countries.
Funding
Abstract
Passive stiffness of the heart is determined largely by extracellular matrix and titin, which functions as a molecular spring within sarcomeres. Titin stiffening is associated with the development of diastolic dysfunction (DD), while augmented titin compliance appears to impair systolic performance in dilated cardiomyopathy. We found that myofibril stiffness was elevated in mice lacking histone deacetylase 6 (HDAC6). Cultured adult murine ventricular myocytes treated with a selective HDAC6 inhibitor also exhibited increased myofibril stiffness. Conversely, HDAC6 overexpression in cardiomyocytes led to decreased myofibril stiffness, as did ex vivo treatment of mouse, rat, and human myofibrils with recombinant HDAC6. Modulation of myofibril stiffness by HDAC6 was dependent on 282 amino acids encompassing a portion of the PEVK element of titin. HDAC6 colocalized with Z-disks, and proteomics analysis suggested that HDAC6 functions as a sarcomeric protein deacetylase. Finally, increased myofibril stiffness in HDAC6-deficient mice was associated with exacerbated DD in response to hypertension or aging. These findings define a role for a deacetylase in the control of myofibril function and myocardial passive stiffness, suggest that reversible acetylation alters titin compliance, and reveal the potential of targeting HDAC6 to manipulate the elastic properties of the heart to treat cardiac diseases.
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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 OpenQuestion graph.