ArticleCirculation2022
Progressive Reduction in Right Ventricular Contractile Function Attributable to Altered Actin Expression in an Aging Mouse Model of Arrhythmogenic Cardiomyopathy.
Article in Circulation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 13 citations in OpenAlex.
- Desmoplakin Loss Leads to PKC- and Src-Mediated Contractile Dysfunction in Cardiomyocytes.Circulation research · 2026Article
- Decreasing Microtubule Detyrosination Improves Cardiac Mechanics and Sodium Channel Function in Arrhythmogenic Cardiomyopathy.Circulation. Arrhythmia and electrophysiology · 2026Article
- Disease models and AAV therapies ofMolecular therapy. Advances · 2026Review
- Generation of aZoological research · 2026Article
- Arrhythmogenic CardiomyopathyGenes · 2025Article
- Lifetime cumulative activity burden is associated with symptomatic heart failure and arrhythmic risk in patients with arrhythmogenic right ventricular cardiomyopathy: a retrospective cohort study.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 · 2024Article
- Dual ablation of the RyR2-Ser2808 and RyR2-Ser2814 sites increases propensity for pro-arrhythmic spontaneous CaThe Journal of physiology · 2024Article
- Mouse Cardiovascular Imaging.Current protocols · 2024Review
- 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
- AAV-Mediated Delivery of Plakophilin-2a Arrests Progression of Arrhythmogenic Right Ventricular Cardiomyopathy in Murine Hearts: Preclinical Evidence Supporting Gene Therapy in Humans.Circulation. Genomic and precision medicine · 2024Article
- Associations of MYPN, TTN, SCN5A, MYO6 and ELN Mutations With Arrhythmias and Subsequent Sudden Cardiac Death: A Case Report of an Ecuadorian Individual.Cardiology research · 2023Article
- The intercalated disc: a unique organelle for electromechanical synchrony in cardiomyocytes.Physiological reviews · 2023Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundArrhythmogenic cardiomyopathy (ACM) is an inherited genetic disorder of desmosomal dysfunction, and PKP2 (plakophilin-2) has been reported to be the most common disease-causing gene when mutation-positive. In the early concealed phase, the ACM heart is at high risk of sudden cardiac death before cardiac remodeling occurs because of mistargeted ion channels and altered Ca
methodsWe studied the outcomes of a human truncating variant of PKP2 on myocyte contraction using a novel knock-in mouse model with insertion of thymidine in exon 5 of
resultsSerial echocardiography of Pkp2 heterozygous (Pkp2-Het) mice revealed progressive failure of the right ventricle (RV) in animals older than 3 months. By contrast, left ventricular function remained normal. ECGs of 6-month-old anesthetized Pkp2-Het mice showed normal baseline heart rates and QRS complexes. Cardiac responses to β-adrenergic agonist isoproterenol (2 mg/kg) plus caffeine (120 mg/kg) were also normal. However, adrenergic stimulation enhanced the susceptibility of Pkp2-Het hearts to tachyarrhythmia and sudden cardiac death. Histological staining showed no significant fibrosis or adipocyte infiltration in the RVs and left ventricles of 6- and 12-month-old Pkp2-Het hearts. Contractility assessment of isolated myocytes demonstrated progressively reduced Pkp2-Het RV cardiomyocyte function consistent with RV failure measured by echocardiography. However, aging Pkp2-Het and control RV myocytes loaded with intracellular Ca
conclusionsDuring the early concealed phase of ACM, reduced actin expression drives loss of RV myocyte contraction, contributing to progressive RV dysfunction.
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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.