ArticleCirculation2021
Arrhythmia Mechanism and Dynamics in a Humanized Mouse Model of Inherited Cardiomyopathy Caused by Phospholamban R14del Mutation.
Article in Circulation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- Optical mapping: pioneering the frontier of preclinical antiarrhythmic drug evaluation.iScience · 2026Review
- Propafenone-mediated gap junctional uncoupling results from aberrant connexin-43 trafficking.Pharmacological reports : PR · 2026Article
- Promoting Autophagy Mitigates Stress-Induced Remodeling in Patient iPSC-CMs with the Phospholamban R9C Mutation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Calcium handling remodeling in dilated cardiomyopathy: From molecular mechanisms to targeted therapies.Channels (Austin, Tex.) · 2025Review
- Remodeling Cardiovascular Research: Ready to Sacrifice Animal Models?Journal of cardiovascular pharmacology · 2025Article
- Targeting Calcium Regulation for Heart Failure and Arrhythmia Therapeutics: A Critical Review.Circulation · 2025Review
- Genetic landscape of phospholamban cardiomyopathies.Frontiers in cell and developmental biology · 2025Review
- Cardiac Applications of CRISPR/AAV-Mediated Precise Genome Editing.bioRxiv : the preprint server for biology · 2024Article
- The network of cardiac KNaunyn-Schmiedeberg's archives of pharmacology · 2024Review
- In Vivo Approaches to Understand Arrhythmogenic Cardiomyopathy: Perspectives on Animal Models.Cells · 2024Review
- Empagliflozin rescues pro-arrhythmic and CaScientific reports · 2024Article
- Quantitative Assessment of Mitochondrial Morphology and Electrophysiological Function in the Diabetic Heart.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Article
- Arrhythmogenic Cardiomyopathy: from Preclinical Models to Genotype-phenotype Correlation and Pathophysiology.Stem cell reviews and reports · 2023Review
- Polyamines from myeloid-derived suppressor cells promote Th17 polarization and disease progression.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Myofilament Alterations Associated with Human R14del-Phospholamban Cardiomyopathy.International journal of molecular sciences · 2023Article
- Isoform changes of action potential regulators in the ventricles of arrhythmogenic phospholamban-R14del humanized mouse hearts.Metabolism: clinical and experimental · 2023Article
- Phospholamban R14del disease: The past, the present and the future.Frontiers in cardiovascular medicine · 2023Review
- Gene editing for cardiomyopathy takes a step forward.Cardiovascular research · 2022Article
- Gene editing reverses arrhythmia susceptibility in humanized PLN-R14del mice: modelling a European cardiomyopathy with global impact.Cardiovascular research · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 7 institutions in 3 countries.
Funding
Abstract
backgroundArginine (Arg) 14 deletion (R14del) in the calcium regulatory protein phospholamban (hPLN
methodsTo address this, we performed high spatiotemporal resolution optical mapping of intact hearts from adult knock-in mice harboring the human PLN
resultsAdverse electrophysiological remodeling was evident in the absence of significant structural or hemodynamic changes. R14del hearts exhibited increased arrhythmia susceptibility compared with wildtype. Underlying this susceptibility was preferential right ventricular action potential prolongation that was unresponsive to β-adrenergic stimulation. A steep repolarization gradient at the left ventricular/right ventricular interface provided the substrate for interventricular activation delays and ultimately local conduction block during rapid pacing. This was followed by the initiation of macroreentrant circuits supporting the onset of ventricular tachycardia. Once sustained, these circuits evolved into high-frequency rotors, which in their majority were pinned to the right ventricle. These rotors exhibited unique spatiotemporal dynamics that promoted their increased stability in R14del compared with wildtype hearts.
conclusionsOur findings highlight the crucial role of primary electric remodeling caused by the hPLN
Indexed as
Identifiers
What OpenQuestion holds
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.