ArticleThe Journal of clinical investigation2021
Targeting the histone demethylase LSD1 prevents cardiomyopathy in a mouse model of laminopathy.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 50 citations in OpenAlex.
- The cardiac 4D nucleome: nuclear and chromatin dynamics across development, disease and ageing.Nature reviews. Cardiology · 2026Review
- Maternal-Fetal Crosstalk in Cardiovascular Programming: Linking the Intrauterine Environment to Lifelong Disease Risk.Journal of cardiovascular development and disease · 2026Review
- Epigenetics, Modifiers, and Molecular Noise: Rethinking Pathophysiology in Dilated and Hypertrophic Cardiomyopathies.International journal of molecular sciences · 2026Review
- Adolescent high fructose consumption induces cardiac dysfunction in adulthood via elevated histone acetylation.Translational pediatrics · 2026Article
- Epigenetic Regulation in Dilated Cardiomyopathy.Heart failure clinics · 2026Review
- 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
- Potential Impact of Parental Origin of Inheritance on the Clinical Presentation of Familial Partial Lipodystrophy Type 2 Syndrome.Clinical endocrinology · 2025Article
- Lamin A/C promotes HBV transcription by modulating histone modification associated with cccDNA minichromosome in an HBx-dependent manner.Virology journal · 2025Article
- Review
- Stem cells in the treatment of myocardial injury-induced cardiomyopathy: mechanisms and efficient utilization strategies.Frontiers in pharmacology · 2025Review
- Non-Cell-Autonomous Cardiomyocyte Regulation Complicates Gene Supplementation Therapy forJACC. Basic to translational science · 2024Article
- Targeting Mitochondria Dysfunction in LMNA Cardiomyopathy.JACC. Basic to translational science · 2024Article
- Perinuclear damage from nuclear envelope deterioration elicits stress responses that contribute toScience advances · 2024Article
- Primate Model Carrying LMNA Mutation Develops Dilated Cardiomyopathy.JACC. Basic to translational science · 2024Article
- Salsolinol improves angiotensin II‑induced myocardial fibrosisExperimental and therapeutic medicine · 2023Article
- An alpha-helix variant p.Arg156Pro in LMNA as a cause of hereditary dilated cardiomyopathy: genetics and bioinfomatics exploration.BMC medical genomics · 2023Article
- Transcriptome studies of inherited dilated cardiomyopathies.Mammalian genome : official journal of the International Mammalian Genome Society · 2023Review
- Epigenetics inCells · 2023Review
- LSD1/PRMT6-targeting gene therapy to attenuate androgen receptor toxic gain-of-function ameliorates spinobulbar muscular atrophy phenotypes in flies and mice.Nature communications · 2023Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
LMNA mutations in patients are responsible for a dilated cardiomyopathy. Molecular mechanisms underlying the origin and development of the pathology are unknown. Herein, using mouse pluripotent embryonic stem cells (ESCs) and a mouse model both harboring the p.H222P Lmna mutation, we found early defects in cardiac differentiation of mutated ESCs and dilatation of mutated embryonic hearts at E13.5, pointing to a developmental origin of the disease. Using mouse ESCs, we demonstrated that cardiac differentiation of LmnaH222P/+ was impaired at the mesodermal stage. Expression of Mesp1, a mesodermal cardiogenic gene involved in epithelial-to-mesenchymal transition of epiblast cells, as well as Snai1 and Twist expression, was decreased in LmnaH222P/+ cells compared with WT cells in the course of differentiation. In turn, cardiomyocyte differentiation was impaired. ChIP assay of H3K4me1 in differentiating cells revealed a specific decrease of this histone mark on regulatory regions of Mesp1 and Twist in LmnaH222P/+ cells. Downregulation or inhibition of LSD1 that specifically demethylated H3K4me1 rescued the epigenetic landscape of mesodermal LmnaH222P/+ cells and in turn contraction of cardiomyocytes. Inhibition of LSD1 in pregnant mice or neonatal mice prevented cardiomyopathy in E13.5 LmnaH222P/H222P offspring and adults, respectively. Thus, LSD1 appeared to be a therapeutic target to prevent or cure dilated cardiomyopathy associated with a laminopathy.
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