ArticleThe Journal of clinical investigation2020
BET bromodomain inhibition attenuates cardiac phenotype in myocyte-specific lamin A/C-deficient mice.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 79 citations in OpenAlex.
- The cardiac 4D nucleome: nuclear and chromatin dynamics across development, disease and ageing.Nature reviews. Cardiology · 2026Review
- BET inhibitors in cardiovascular diseases: from atherosclerosis to heart failure.Pharmacological reports : PR · 2026Review
- Epigenetic regulation of cardiac physiology and pathophysiology: biological sex matters.The journal of cardiovascular aging · 2026Article
- Perinuclear organelle trauma at the nexus of cardiomyopathy pathogenesis arising from loss of functionNucleus (Austin, Tex.) · 2025Review
- LMNA-related cardiomyopathy: From molecular pathology to cardiac gene therapy.Journal of advanced research · 2025Review
- BET Inhibitor JQ1 Attenuates Atrial Fibrillation Through Modulation of Fibrosis, Calcium Homeostasis, and Mitochondrial Function in a Murine Model.International journal of molecular sciences · 2025Article
- Lamin A/C Expression in Hematopoietic Cells Declines During Human Aging and Constrains Atherosclerosis in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- DNA double-stranded breaks, a hallmark of aging, defined at the nucleotide resolution, are increased and associated with transcription in the cardiac myocytes in LMNA-cardiomyopathy.Cardiovascular research · 2025Article
- Lamin: guardian against DNA damage by transcription stress.Cardiovascular research · 2025Article
- Cardiomyocyte cytosolic nuclear self-DNA contributes to the pathogenesis of desmoplakin cardiomyopathy.JCI insight · 2025Article
- Knowledge, attitudes, and practices regarding heart failure among Chinese patients: a cross-sectional study.BMC public health · 2025Article
- (+)-JQ-1 alleviates cardiac injury in myocardial infarction by inhibiting ferroptosis through the NAMPT/SIRT1 pathway.Cell death & disease · 2025Article
- Lamin variants cause cardiac arrhythmogenicity in Drosophila.Disease models & mechanisms · 2025Article
- Epigenetic Drivers of Atrial Fibrillation: Mechanisms, Biomarkers, and Therapeutic Targets.International journal of molecular sciences · 2025Review
- Cardiac phenotypes in LMNA mutations.Current opinion in cardiology · 2025Review
- Phenotypic diversity of the LMNA mutations.Current opinion in cardiology · 2025Article
- NLRP3 Inflammasome Targeting Offers a Novel Therapeutic Paradigm for Sepsis-Induced Myocardial Injury.Drug design, development and therapy · 2025Review
- Non-Cell-Autonomous Cardiomyocyte Regulation Complicates Gene Supplementation Therapy forJACC. Basic to translational science · 2024Article
- Article
- BRD4: an effective target for organ fibrosis.Biomarker research · 2024Review
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8 authors at 3 institutions in 1 country.
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Abstract
Mutation in the LMNA gene, encoding lamin A/C, causes a diverse group of diseases called laminopathies. Cardiac involvement is the major cause of death and manifests as dilated cardiomyopathy, heart failure, arrhythmias, and sudden death. There is no specific therapy for LMNA-associated cardiomyopathy. We report that deletion of Lmna in cardiomyocytes in mice leads to severe cardiac dysfunction, conduction defect, ventricular arrhythmias, fibrosis, apoptosis, and premature death within 4 weeks. The phenotype is similar to LMNA-associated cardiomyopathy in humans. RNA sequencing, performed before the onset of cardiac dysfunction, led to identification of 2338 differentially expressed genes (DEGs) in Lmna-deleted cardiomyocytes. DEGs predicted activation of bromodomain-containing protein 4 (BRD4), a regulator of chromatin-associated proteins and transcription factors, which was confirmed by complementary approaches, including chromatin immunoprecipitation sequencing. Daily injection of JQ1, a specific BET bromodomain inhibitor, partially reversed the DEGs, including those encoding secretome; improved cardiac function; abrogated cardiac arrhythmias, fibrosis, and apoptosis; and prolonged the median survival time 2-fold in the myocyte-specific Lmna-deleted mice. The findings highlight the important role of LMNA in cardiomyocytes and identify BET bromodomain inhibition as a potential therapeutic target in LMNA-associated cardiomyopathy, for which there is no specific effective therapy.
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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.