ArticleScience translational medicine2014
Identification of a new modulator of the intercalated disc in a zebrafish model of arrhythmogenic cardiomyopathy.
Article in Science translational medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT06174220 (Targeted Therapy With Glycogen Synthase Kinase-3 Inhibition for Arrhythmogenic Cardiomyopathy), which is not on this map. Cited by 155 papers.
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.
Targeted Therapy With Glycogen Synthase Kinase-3 Inhibition for Arrhythmogenic Cardiomyopathy
Who cites it
155 citing papers in PubMed, 271 citations in OpenAlex.
- Single nucleus RNA sequencing identifies PLXNA4 upregulation in end-stage arrhythmogenic right ventricular cardiomyopathy.iScience · 2026Article
- Zebrafish dspb-/- mutant as a model for non-dilated left ventricular cardiomyopathy: exploring cardiac dysfunction and exercise modulation.Molecular biomedicine · 2026Article
- Epigenetic and chromatin remodeling mechanisms across cardiomyopathies: a comprehensive review.Epigenetics & chromatin · 2026Review
- Review
- Cardiomyocyte-Specific Plakophilin-2 Loss Is Sufficient to Induce Aging and Senescence of Nonmyocytes: Relevance to Arrhythmogenic Cardiomyopathy.Journal of the American Heart Association · 2026Article
- Novel PKP2 compound heterozygous mutations causing neonatal early-onset arrhythmogenic cardiomyopathy: insights into the synergistic pathogenicity of biallelic inactivation.Functional & integrative genomics · 2026Article
- Zebrafish in Cardiovascular Disease Research: from Model to Application.International journal of biological sciences · 2026Review
- Towards Mechanism-Based Therapies in Arrhythmogenic Cardiomyopathy.JACC. Basic to translational science · 2025Article
- Evaluation of Tideglusib as a Disease Modifying Therapy in Murine Models of Arrhythmogenic Cardiomyopathy.JACC. Basic to translational science · 2025Article
- Zebrafish Models of Induced Lymphangiogenesis: Current Advancements and Therapeutic Discovery.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Computational Modeling of Effects ofCirculation. Arrhythmia and electrophysiology · 2025Article
- Inhibition of Soluble Epoxide Hydrolase Reduces Inflammation and Myocardial Injury in Arrhythmogenic Cardiomyopathy.JACC. Basic to translational science · 2025Article
- Cardiac sympathetic neurons are additional cells affected in genetically determined arrhythmogenic cardiomyopathy.The Journal of physiology · 2025Article
- Identification of key autophagy-related genes in arrhythmogenic right ventricular cardiomyopathy through gene expression profiling.Medicine · 2025Article
- Naxos Disease and Related Cardio-Cutaneous Syndromes.JACC. Advances · 2025Review
- Hot Phases Cardiomyopathy: Pathophysiology, Diagnostic Challenges, and Emerging Therapies.Current cardiology reports · 2025Review
- Describing and Mapping the Research Trend of Scientific Publications on Arrhythmogenic Right Ventricular Cardiomyopathy Across Four Decades: A Bibliometric Analysis.Clinical cardiology · 2024Article
- In Vivo Approaches to Understand Arrhythmogenic Cardiomyopathy: Perspectives on Animal Models.Cells · 2024Review
- Animal Models and Molecular Pathogenesis of Arrhythmogenic Cardiomyopathy Associated with Pathogenic Variants in Intercalated Disc Genes.International journal of molecular sciences · 2024Review
- NFĸB signaling drives myocardial injury via CCR2+ macrophages in a preclinical model of arrhythmogenic cardiomyopathy.The Journal of clinical investigation · 2024Article
95 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
14 authors at 4 institutions in 1 country.
Funding
Abstract
Arrhythmogenic cardiomyopathy (ACM) is characterized by frequent cardiac arrhythmias. To elucidate the underlying mechanisms and discover potential chemical modifiers, we created a zebrafish model of ACM with cardiac myocyte-specific expression of the human 2057del2 mutation in the gene encoding plakoglobin. A high-throughput screen identified SB216763 as a suppressor of the disease phenotype. Early SB216763 therapy prevented heart failure and reduced mortality in the fish model. Zebrafish ventricular myocytes that expressed 2057del2 plakoglobin exhibited 70 to 80% reductions in I(Na) and I(K1) current densities, which were normalized by SB216763. Neonatal rat ventricular myocytes that expressed 2057del2 plakoglobin recapitulated pathobiological features seen in patients with ACM, all of which were reversed or prevented by SB216763. The reverse remodeling observed with SB216763 involved marked subcellular redistribution of plakoglobin, connexin 43, and Nav1.5, but without changes in their total cellular content, implicating a defect in protein trafficking to intercalated discs. In further support of this mechanism, we observed SB216763-reversible, abnormal subcellular distribution of SAP97 (a protein known to mediate forward trafficking of Nav1.5 and Kir2.1) in rat cardiac myocytes expressing 2057del2 plakoglobin and in cardiac myocytes derived from induced pluripotent stem cells from two ACM probands with plakophilin-2 mutations. These observations pinpoint aberrant trafficking of intercalated disc proteins as a central mechanism in ACM myocyte injury and electrical abnormalities.
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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 Socratic graph.