ArticleEuropean heart journal2022
Role of plakophilin-2 expression on exercise-related progression of arrhythmogenic right ventricular cardiomyopathy: a translational study.
Article in European heart journal, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 24 papers.
What it found
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Who cites it
24 citing papers in PubMed, 42 citations in OpenAlex.
- Physical Activity in Arrhythmogenic Cardiomyopathy: From Trigger to Therapeutic Dilemma.Reviews in cardiovascular medicine · 2026Review
- Lipid Metabolism as a Therapeutic Target in Arrhythmogenic Cardiomyopathy: Emerging Therapeutic Implications of Lipid-Lowering Therapy.Reviews in cardiovascular medicine · 2026Review
- Decreasing Microtubule Detyrosination Improves Cardiac Mechanics and Sodium Channel Function in Arrhythmogenic Cardiomyopathy.Circulation. Arrhythmia and electrophysiology · 2026Article
- 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
- Disease models and AAV therapies ofMolecular therapy. Advances · 2026Review
- Genome-First Arrhythmogenic Right Ventricular Cardiomyopathy Penetrance Is Not Correlated With Lifetime Exercise History.JACC. Advances · 2026Article
- Exercise-induced dysregulation of the adrenergic response in a mouse model of PKP2-arrhythmogenic cardiomyopathy.Heart rhythm · 2025Article
- Atrial cardiomyopathy resulting from loss of plakophilin-2 expression: Response to adrenergic stimulation and implications for the exercise response.The Journal of physiology · 2025Article
- Epicardial adipose tissue: a new link between type 2 diabetes and heart failure-a comprehensive review.Heart failure reviews · 2025Review
- Meeting report - Alpine desmosome disease meeting 2024: advances and emerging topics in desmosomes and related diseases.Journal of cell science · 2025Article
- High-Fat Diet Augments Myocardial Inflammation and Cardiac Dysfunction in Arrhythmogenic Cardiomyopathy.Nutrients · 2024Article
- Detection of gene mutation in the prognosis of a patient with arrhythmogenic right ventricular cardiomyopathy: a case report.Journal of medical case reports · 2024Article
- Overexpression of Plakophilin2 Mitigates Capillary Leak Syndrome in Severe Acute Pancreatitis by Activating the p38/MAPK Signaling Pathway.Journal of inflammation research · 2024Article
- The intercalated disc: a unique organelle for electromechanical synchrony in cardiomyocytes.Physiological reviews · 2023Review
- ELITE: rationale and design of a longitudinal elite athlete, extreme cardiovascular phenotyping, prospective cohort study.BMJ open sport & exercise medicine · 2023Article
- CaJournal of translational medicine · 2022Article
- Arrhythmogenic right-ventricular cardiomyopathy with plakophilin-2 genetic variant concomitant with early manifestation of ventricular tachyarrhythmia: a case series.European heart journal. Case reports · 2022Article
- Loss of Nuclear Envelope Integrity and Increased Oxidant Production Cause DNA Damage in Adult Hearts Deficient in PKP2: A Molecular Substrate of ARVC.Circulation · 2022Article
- Sex-Related Differences in Genetic Cardiomyopathies.Journal of the American Heart Association · 2022Review
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
20 authors at 7 institutions in 6 countries.
Funding
Abstract
aimsExercise increases arrhythmia risk and cardiomyopathy progression in arrhythmogenic right ventricular cardiomyopathy (ARVC) patients, but the mechanisms remain unknown. We investigated transcriptomic changes caused by endurance training in mice deficient in plakophilin-2 (PKP2cKO), a desmosomal protein important for intercalated disc formation, commonly mutated in ARVC and controls. METHODS AND
resultsExercise alone caused transcriptional downregulation of genes coding intercalated disk proteins. The changes converged with those in sedentary and in exercised PKP2cKO mice. PKP2 loss caused cardiac contractile deficit, decreased muscle mass and increased functional/transcriptomic signatures of apoptosis, despite increased fractional shortening and calcium transient amplitude in single myocytes. Exercise accelerated cardiac dysfunction, an effect dampened by pre-training animals prior to PKP2-KO. Consistent with PKP2-dependent muscle mass deficit, cardiac dimensions in human athletes carrying PKP2 mutations were reduced, compared to matched controls.
conclusionsWe speculate that exercise challenges a cardiomyocyte "desmosomal reserve" which, if impaired genetically (e.g., PKP2 loss), accelerates progression of cardiomyopathy.
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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.