ArticleThe Journal of clinical investigation2006
Suppression of canonical Wnt/beta-catenin signaling by nuclear plakoglobin recapitulates phenotype of arrhythmogenic right ventricular cardiomyopathy.
Article in The Journal of clinical investigation, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 339 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
339 citing papers in PubMed, 2 syntheses or guidelines pooled it, 612 citations in OpenAlex.
- Pooled it
- Facts and Gaps in Exercise Influence on Arrhythmogenic Cardiomyopathy: New Insights From a Meta-Analysis Approach.Frontiers in cardiovascular medicine · 2021Pooled it
- PKP2 orchestrates OXPHOS expression in cardiomyocytes via a PGC1α-dependent mechanism.Cardiovascular research · 2026Article
- Desmoplakin Loss Leads to PKC- and Src-Mediated Contractile Dysfunction in Cardiomyocytes.Circulation research · 2026Article
- FASN-mediatediScience · 2026Article
- Periostin-CCL3 Feedforward Signaling Loop Promotes Cardiac Fibrosis and Cardiomyocyte Necroptosis in Arrhythmogenic Cardiomyopathy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Desmoplakin loss in alveolar epithelium drives Wnt/β-Catenin-mediated extracellular matrix remodeling and fibrotic signaling in vitro.Molecular biology reports · 2026Article
- Lipid Metabolism as a Therapeutic Target in Arrhythmogenic Cardiomyopathy: Emerging Therapeutic Implications of Lipid-Lowering Therapy.Reviews in cardiovascular medicine · 2026Review
- Epigenetic and chromatin remodeling mechanisms across cardiomyopathies: a comprehensive review.Epigenetics & chromatin · 2026Review
- Interleukin-1β Drives Disease Progression in Arrhythmogenic Cardiomyopathy.JACC. Basic to translational science · 2026Article
- Identification and Verification of SLC6A15 Involved in Keloid via Bioinformatics Analysis and Machine Learning.Biochemical genetics · 2026Article
- Review
- An Atypical "Hot-Phase" ARVC in a PKP2 Carrier.JACC. Case reports · 2026Article
- Novel PKP2 compound heterozygous mutations causing neonatal early-onset arrhythmogenic cardiomyopathy: insights into the synergistic pathogenicity of biallelic inactivation.Functional & integrative genomics · 2026Article
- Identification of Key Genes and Pathways Associated With Gender Differences in Pulmonary Arterial Hypertension Based on Bioinformatic Approaches.BioMed research international · 2026Article
- Adipocyte-specific ablation of plakoglobin in mice does not affect adiposity but results in sexual-dimorphic effects on weight gain.Physiological reports · 2025Article
- Modelling arrhythmogenic cardiomyopathy fattyfibro pathology with PKP2-deficient epicardial cells derived from human iPSCs.Communications biology · 2025Article
- Molecular Pathogenesis of Arrhythmogenic Cardiomyopathy: Mechanisms and Therapeutic Perspectives.Biomolecules · 2025Review
- Tailored therapeutics for cardiomyopathies.Nature reviews. Cardiology · 2025Review
- Comprehensive analysis of desmosomal protein remodelling identifies desmocollin-2 as potential biomarker for arrhythmogenic cardiomyopathy.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2025Article
279 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVC) is a genetic disease caused by mutations in desmosomal proteins. The phenotypic hallmark of ARVC is fibroadipocytic replacement of cardiac myocytes, which is a unique phenotype with a yet-to-be-defined molecular mechanism. We established atrial myocyte cell lines expressing siRNA against desmoplakin (DP), responsible for human ARVC. We show suppression of DP expression leads to nuclear localization of the desmosomal protein plakoglobin and a 2-fold reduction in canonical Wnt/beta-catenin signaling through Tcf/Lef1 transcription factors. The ensuing phenotype is increased expression of adipogenic and fibrogenic genes and accumulation of fat droplets. We further show that cardiac-restricted deletion of Dsp, encoding DP, impairs cardiac morphogenesis and leads to high embryonic lethality in the homozygous state. Heterozygous DP-deficient mice exhibited excess adipocytes and fibrosis in the myocardium, increased myocyte apoptosis, cardiac dysfunction, and ventricular arrhythmias, thus recapitulating the phenotype of human ARVC. We believe our results provide for a novel molecular mechanism for the pathogenesis of ARVC and establish cardiac-restricted DP-deficient mice as a model for human ARVC. These findings could provide for the opportunity to identify new diagnostic markers and therapeutic targets in patients with ARVC.
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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.