ArticleJCI insight2017
Reversal of pathological cardiac hypertrophy via the MEF2-coregulator interface.
Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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.
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Who cites it
22 citing papers in PubMed, 42 citations in OpenAlex.
- Immature and mature myocardium in the pathophysiology of hypertrophic cardiomyopathy.Journal of molecular and cellular cardiology plus · 2026Review
- The Diverse Roles of the MEF2 Transcription Factor Family in Tumor Progression and Emerging Therapeutic Opportunities.Biomedicines · 2026Review
- Nanoparticle-Based Therapeutic Strategies for Pathological Cardiac Hypertrophy: Preclinical Advances, Translational Challenges, and Future Perspectives.International journal of nanomedicine · 2026Review
- HDAC5 Inhibition as a Therapeutic Strategy for Titin Deficiency-Induced Cardiac Remodeling: Insights from Human iPSC Models.Medicines (Basel, Switzerland) · 2025Article
- Mitochondrial Reactive Oxygen Species Dysregulation in Heart Failure with Preserved Ejection Fraction: A Fraction of the Whole.Antioxidants (Basel, Switzerland) · 2024Review
- Article
- SWAP70 Overexpression Protects Against Pathological Cardiac Hypertrophy in a TAK1-Dependent Manner.Journal of the American Heart Association · 2023Article
- A family with brachydactyly mental retardation syndrome with a missense variant inClinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2023Article
- CaMKII Splice Variants in Vascular Smooth Muscle Cells: The Next Step or Redundancy?International journal of molecular sciences · 2022Review
- Epigenetic remodeling in heart failure with preserved ejection fraction.Current opinion in cardiology · 2022Review
- Transcriptomic and genomic studies classify NKL54 as a histone deacetylase inhibitor with indirect influence on MEF2-dependent transcription.Nucleic acids research · 2022Article
- Stachydrine hydrochloride ameliorates cardiac hypertrophy through CaMKII/HDAC4/MEF2C signal pathway.American journal of translational research · 2022Article
- Interactions between the ERK1/2 signaling pathway and PCAF play a key role in PE‑induced cardiomyocyte hypertrophy.Molecular medicine reports · 2021Article
- The CaeLife · 2021Article
- Review
- Leveraging clinical epigenetics in heart failure with preserved ejection fraction: a call for individualized therapies.European heart journal · 2021Review
- Cardiac Gq Receptors and Calcineurin Activation Are Not Required for the Hypertrophic Response to Mechanical Left Ventricular Pressure Overload.Frontiers in cell and developmental biology · 2021Article
- MEF2D sustains activation of effector Foxp3+ Tregs during transplant survival and anticancer immunity.The Journal of clinical investigation · 2020Article
- Hematopoietic Stem Cell Transcription Factors in Cardiovascular Pathology.Frontiers in genetics · 2020Review
- Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Cardiac hypertrophy, as a response to hemodynamic stress, is associated with cardiac dysfunction and death, but whether hypertrophy itself represents a pathological process remains unclear. Hypertrophy is driven by changes in myocardial gene expression that require the MEF2 family of DNA-binding transcription factors, as well as the nuclear lysine acetyltransferase p300. Here we used genetic and small-molecule probes to determine the effects of preventing MEF2 acetylation on cardiac adaptation to stress. Both nonacetylatable MEF2 mutants and 8MI, a molecule designed to interfere with MEF2-coregulator binding, prevented hypertrophy in cultured cardiac myocytes. 8MI prevented cardiac hypertrophy in 3 distinct stress models, and reversed established hypertrophy in vivo, associated with normalization of myocardial structure and function. The effects of 8MI were reversible, and did not prevent training effects of swimming. Mechanistically, 8MI blocked stress-induced MEF2 acetylation, nuclear export of class II histone deacetylases HDAC4 and -5, and p300 induction, without impeding HDAC4 phosphorylation. Correspondingly, 8MI transformed the transcriptional response to pressure overload, normalizing almost all 232 genes dysregulated by hemodynamic stress. We conclude that MEF2 acetylation is required for development and maintenance of pathological cardiac hypertrophy, and that blocking MEF2 acetylation can permit recovery from hypertrophy without impairing physiologic adaptation.
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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.