ArticleJournal of the American Heart Association2018
Gene Transfer of Engineered Calmodulin Alleviates Ventricular Arrhythmias in a Calsequestrin-Associated Mouse Model of Catecholaminergic Polymorphic Ventricular Tachycardia.
Article in Journal of the American Heart Association, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 46 citations in OpenAlex.
- An International Multicenter Evaluation of Inheritance Patterns, Arrhythmic Risks, and Underlying Mechanisms ofCirculation · 2020Trial
- Local calcium dynamics and signalling in cardiomyocytes.Nature reviews. Cardiology · 2026Review
- Dynamic-Structure Redesign of Calmodulin Reveals Mechanistic Constraints on Ryr2 Regulation.bioRxiv : the preprint server for biology · 2026Article
- Gene therapy for cardiac arrhythmias.Nature reviews. Cardiology · 2026Review
- Gene Therapy for Cardiac Arrhythmias: Mechanisms, Modalities and Therapeutic Applications.Medical sciences (Basel, Switzerland) · 2025Review
- Distinct intracellular spatiotemporal expression of Calmodulin genes underlies functional diversity of Calmodulin-dependent signalling in cardiac myocytes.Cardiovascular research · 2025Article
- Catecholaminergic Polymorphic Ventricular Tachycardia: Advancing From Molecular Insights to Preclinical Models.Journal of the American Heart Association · 2025Review
- Catecholaminergic Polymorphic Ventricular Tachycardia: Clinical Characteristics, Diagnostic Evaluation and Therapeutic Strategies.Journal of clinical medicine · 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
- Molecular Insights into the MLCK Activation by CaM.Journal of chemical information and modeling · 2023Article
- The Dysfunction of CaInternational journal of molecular sciences · 2023Review
- EuBiophysical journal · 2023Article
- Article
- Non-Canonical Interaction between Calmodulin and Calcineurin Contributes to the Differential Regulation of Plant-Derived Calmodulins on Calcineurin.Journal of chemical information and modeling · 2021Article
- Recent advances in gene therapy for atrial fibrillation.Journal of cardiovascular electrophysiology · 2021Review
- Ventricular voltage-gated ion channels: Detection, characteristics, mechanisms, and drug safety evaluation.Clinical and translational medicine · 2021Review
- The role of calcium homeostasis remodeling in inherited cardiac arrhythmia syndromes.Pflugers Archiv : European journal of physiology · 2021Review
- Advances in the Molecular Genetics of Catecholaminergic Polymorphic Ventricular Tachycardia.Frontiers in pharmacology · 2021Review
- Molecular and tissue mechanisms of catecholaminergic polymorphic ventricular tachycardia.The Journal of physiology · 2020Review
- The arrhythmogenic N53I variant subtly changes the structure and dynamics in the calmodulin N-terminal domain, altering its interaction with the cardiac ryanodine receptor.The Journal of biological chemistry · 2020Article
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundCatecholaminergic polymorphic ventricular tachycardia (CPVT) is a familial arrhythmogenic syndrome characterized by sudden death. There are several genetic forms of CPVT associated with mutations in genes encoding the cardiac ryanodine receptor (RyR2) and its auxiliary proteins including calsequestrin (CASQ2) and calmodulin (CaM). It has been suggested that impairment of the ability of RyR2 to stay closed (ie, refractory) during diastole may be a common mechanism for these diseases. Here, we explore the possibility of engineering CaM variants that normalize abbreviated RyR2 refractoriness for subsequent viral-mediated delivery to alleviate arrhythmias in non-CaM-related CPVT. METHODS AND
resultsTo that end, we have designed a CaM protein (GSH-M37Q; dubbed as therapeutic CaM or T-CaM) that exhibited a slowed N-terminal Ca dissociation rate and prolonged RyR2 refractoriness in permeabilized myocytes derived from CPVT mice carrying the CASQ2 mutation R33Q. This T-CaM was introduced to the heart of R33Q mice through recombinant adeno-associated viral vector serotype 9. Eight weeks postinfection, we performed confocal microscopy to assess Ca handling and recorded surface ECGs to assess susceptibility to arrhythmias in vivo. During catecholamine stimulation with isoproterenol, T-CaM reduced isoproterenol-promoted diastolic Ca waves in isolated CPVT cardiomyocytes. Importantly, T-CaM exposure abolished ventricular tachycardia in CPVT mice challenged with catecholamines.
conclusionsOur results suggest that gene transfer of T-CaM by adeno-associated viral vector serotype 9 improves myocyte Ca handling and alleviates arrhythmias in a calsequestrin-associated CPVT model, thus supporting the potential of a CaM-based antiarrhythmic approach as a therapeutic avenue for genetically distinct forms of CPVT.
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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.