ArticleJournal of cellular and molecular medicine2009
Abnormal connexin43 in arrhythmogenic right ventricular cardiomyopathy caused by plakophilin-2 mutations.
Article in Journal of cellular and molecular medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 93 citations in OpenAlex.
- Practical guidelines for rigor and reproducibility in preclinical and clinical studies on cardioprotection.Basic research in cardiology · 2018Guideline
- Propafenone-mediated gap junctional uncoupling results from aberrant connexin-43 trafficking.Pharmacological reports : PR · 2026Article
- Connexin-43 Restoration Alleviates Desmosomal Arrhythmogenic Cardiomyopathy.Circulation. Heart failure · 2026Article
- Epigenetic regulation of electromechanical continuity might determine phenotypic heterogeneity in SCN5A mutation carriers in Brugada syndrome.Scientific reports · 2025Article
- KCNQ1 and GJA1 Variants Associated With Arrhythmogenic Right Ventricular Cardiomyopathy With a Lethal Outcome.JACC. Case reports · 2025Article
- Computational Modeling of Effects ofCirculation. Arrhythmia and electrophysiology · 2025Article
- Cardiomyocyte and stromal cell cross-talk influences the pathogenesis of arrhythmogenic cardiomyopathy: a multi-level analysis uncovers DLK1-NOTCH pathway role in fibro-adipose remodelling.Cell death discovery · 2024Article
- Engineered tissue geometry and Plakophilin-2 regulate electrophysiology of human iPSC-derived cardiomyocytes.APL bioengineering · 2024Article
- Arrhythmogenic Cardiomyopathy: from Preclinical Models to Genotype-phenotype Correlation and Pathophysiology.Stem cell reviews and reports · 2023Review
- Cheek-Pro-Heart: What Can the Buccal Mucosa Do for Arrhythmogenic Cardiomyopathy?Biomedicines · 2023Review
- Advances in Ion Channel, Non-Desmosomal Variants and Autophagic Mechanisms Implicated in Arrhythmogenic Cardiomyopathy.Current issues in molecular biology · 2023Review
- Alterations in Calcium Handling Are a Common Feature in an Arrhythmogenic Cardiomyopathy Cell Model Triggered by Desmosome Genes Loss.International journal of molecular sciences · 2023Article
- Modeling incomplete penetrance in arrhythmogenic cardiomyopathy by human induced pluripotent stem cell derived cardiomyocytes.Computational and structural biotechnology journal · 2023Article
- Arrhythmogenic Cardiomyopathy: Exercise Pitfalls, Role of Connexin-43, and Moving beyond Antiarrhythmics.International journal of molecular sciences · 2022Review
- Analysis of buccal mucosa as a prognostic tool in children with arrhythmogenic cardiomyopathy.Progress in pediatric cardiology · 2022Article
- Desmosomes: emerging pathways and non-canonical functions in cardiac arrhythmias and disease.Biophysical reviews · 2021Review
- The p.Ala2430Val mutation in filamin C causes a "hypertrophic myofibrillar cardiomyopathy".Journal of muscle research and cell motility · 2021Article
- Mechanisms of Arrhythmias in the Brugada Syndrome.International journal of molecular sciences · 2020Review
- Arrhythmogenic cardiomyopathy: pathogenesis, pro-arrhythmic remodelling, and novel approaches for risk stratification and therapy.Cardiovascular research · 2020Review
- Molecular mechanisms of arrhythmogenic cardiomyopathy.Nature reviews. Cardiology · 2019Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disorder of cardiomyocyte intercalated disk proteins causing sudden death. Heterozygous mutations of the desmosomal protein plakophilin-2 (PKP-2) are the commonest genetic cause of ARVC. Abnormal gap junction connexin43 expression has been reported in autosomal dominant forms of ARVC (Naxos and Carvajal disease) caused by homozygous mutations of desmosomal plakoglobin and desmoplakin. In tissue culture, suppression of PKP-2 results in decreased expression of connexin43. We sought to characterize the expression and localization of connexin43 in patients with ARVC secondary to heterozygous PKP-2 mutations. Complete PKP-2 gene sequencing of 27 ARVC patients was utilized to identify mutant genotypes. Endomyocardial biopsies of identified carriers were then assessed by immunofluorescence to visualize intercalated disk proteins. N-cadherin was targeted to highlight intercalated disks, followed by counterstaining for PKP-2 or connexin43 using confocal double immunofluorescence microscopy. Immunofluorescence was quantified using an AdobeA Photoshop protocol, and colocalization coefficients were determined. PKP-2 siRNA experiments were performed in mouse cardiomyocyte (HL1) cell culture with Western blot analysis to assess connexin43 expression following PKP-2 suppression. Missense and frameshift mutations of the PKP-2 gene were found in four patients with biopsy material available for analysis. Immunofluorescent studies showed PKP-2 localization to the intercalated disk despite mutations, but associated with decreased connexin43 expression and abnormal colocalization. PKP-2 siRNA in HL1 culture confirmed decreased connexin43 expression. Reduced connexin43 expression and localization to the intercalated disk occurs in heterozygous human PKP-2 mutations, potentially explaining the delayed conduction and propensity to develop arrhythmias seen in this disease.
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