ArticleThe Journal of clinical investigation2019
Ankyrin-B dysfunction predisposes to arrhythmogenic cardiomyopathy and is amenable to therapy.
Registry-linked trialOpen access · bronzeAbstract read
In one paragraph
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06174220 (Targeted Therapy With Glycogen Synthase Kinase-3 Inhibition for Arrhythmogenic Cardiomyopathy), which is not on this map. Cited by 40 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
40citing papers in PubMed, 1 pooled it
4.7field-weighted citation impact, top 4% of its field
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.
Targeted Therapy With Glycogen Synthase Kinase-3 Inhibition for Arrhythmogenic Cardiomyopathy
Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
- Meta-analysis of Transcriptomic Data Reveals Pathophysiological Modules Involved with Atrial Fibrillation.Molecular diagnosis & therapy · 2020Pooled it
- Early-onset and rapid progression of arrhythmogenic cardiomyopathy in a pediatric patient with medium chain acyl-CoA dehydrogenase deficiency.HeartRhythm case reports · 2026Article
- Mitochondrial Adaptation to Mechanical Stress in Cardiac Ageing and Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Zebrafish in Cardiovascular Disease Research: from Model to Application.International journal of biological sciences · 2026Review
- Molecular mechanisms and intervention approaches of heart failure (Review).International journal of molecular medicine · 2025Review
- Evaluation of Tideglusib as a Disease Modifying Therapy in Murine Models of Arrhythmogenic Cardiomyopathy.JACC. Basic to translational science · 2025Article
- Towards Mechanism-Based Therapies in Arrhythmogenic Cardiomyopathy.JACC. Basic to translational science · 2025Article
- Targeting Canonical Wnt-signaling Through GSK-3β in Arrhythmogenic Cardiomyopathy: Conservative or Progressive?Journal of cardiovascular translational research · 2025Review
- Reappraisal ofReviews in cardiovascular medicine · 2025Review
- Left Ventricular Non-Compaction, Atrial Fibrillation andJournal of clinical medicine research · 2025Article
- Describing and Mapping the Research Trend of Scientific Publications on Arrhythmogenic Right Ventricular Cardiomyopathy Across Four Decades: A Bibliometric Analysis.Clinical cardiology · 2024Article
- Physical and functional convergence of the autism risk genes Scn2a and Ank2 in neocortical pyramidal cell dendrites.Neuron · 2024Article
- Molecular Pathways and Animal Models of Arrhythmias.Advances in experimental medicine and biology · 2024Article
- Genetic inactivation of β-catenin is salubrious, whereas its activation is deleterious in desmoplakin cardiomyopathy.Cardiovascular research · 2023Article
- Ankyrin B promotes developmental spine regulation in the mouse prefrontal cortex.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- Impact of stress on cardiac phenotypes in mice harboring an ankyrin-B disease variant.The Journal of biological chemistry · 2023Article
- Genetics of sinoatrial node function and heart rate disorders.Disease models & mechanisms · 2023Review
- Study of pathogenic genes in a pedigree with familial dilated cardiomyopathy.World journal of clinical cases · 2023Article
- Sinus node dysfunction: current understanding and future directions.American journal of physiology. Heart and circulatory physiology · 2023Review
- The recent progress of peptide regulators for the Wnt/β-catenin signaling pathway.Frontiers in medicine · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
56 authors at 20 institutions in 7 countries.
Jason D RobertsSection of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, Western University, London, Ontario, Canada.
Nathaniel P MurphyDorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
Robert M HamiltonThe Labatt Family Heart Centre (Department of Pediatrics) and Translational Medicine, The Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada.
Ellen R LubbersDorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
Cynthia A JamesDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Crystal F KlineDorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
Michael H GollobPeter Munk Cardiac Centre, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada.
Andrew D KrahnHeart Rhythm Services, Division of Cardiology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
Amy C SturmGenomic Medicine Institute, Geisinger, Danville, Pennsylvania, USA.
Hassan MusaDorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
Mona El-RefaeyDorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
Sara KoenigDorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
Meriam Åström AneqDepartment of Clinical Physiology and Department of Medical and Health Sciences, Linköping University, Linköping, Sweden.
Edgar T HoorntjeNetherlands Heart Institute, Utrecht, Netherlands.
Sharon L GrawCardiovascular Institute and Adult Medical Genetics Program, University of Colorado Denver, Aurora, Colorado, USA.
Robert W DaviesProgram in Genetics and Genome Biology and The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada.
Muhammad Arshad RafiqThe Labatt Family Heart Centre (Department of Pediatrics) and Translational Medicine, The Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada.
Tamara T KoopmannThe Labatt Family Heart Centre (Department of Pediatrics) and Translational Medicine, The Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada.
Shabana AafaqiThe Labatt Family Heart Centre (Department of Pediatrics) and Translational Medicine, The Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada.
Meena FatahThe Labatt Family Heart Centre (Department of Pediatrics) and Translational Medicine, The Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada.
David A ChiassonPediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Ontario, Canada.
Matthew Rg TaylorCardiovascular Institute and Adult Medical Genetics Program, University of Colorado Denver, Aurora, Colorado, USA.
Samantha L SimmonsDorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
Mei HanDorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
Chantal Jm van OpbergenDepartment of Medical Physiology, Division of Heart and Lungs, University Medical Center, Utrecht, Utrecht University, Utrecht, Netherlands.
Loren E WoldDorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
Gianfranco SinagraCardiovascular Department, ASUITS University of Trieste, Trieste, Italy.
Kirti MittalThe Labatt Family Heart Centre (Department of Pediatrics) and Translational Medicine, The Hospital for Sick Children and the University of Toronto, Toronto, Ontario, Canada.
Crystal TichnellDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Brittney MurrayDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Alberto CodimaDepartment of Medicine, University of Sao Paulo, Sao Paulo, Brazil.
Babak NazerKnight Cardiovascular Institute, Oregon Health and Science University, Portland, Oregon, USA.
Duy T NguyenSection of Cardiac Electrophysiology, Division of Cardiology, University of Colorado, Aurora, Colorado, USA.
Frank I MarcusDivision of Cardiology, Sarver Heart Center, University of Arizona, Tucson, Arizona, USA.
Nara SobrieraMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Elisabeth M LodderAmsterdam University Medical Center, University of Amsterdam, Heart Centre, Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam, Netherlands.
Maarten P van den BergDepartment of Cardiology, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands.
Danna A SpearsPeter Munk Cardiac Centre, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada.
John F RobinsonRobarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
Philip C UrsellDepartment of Pathology, UCSF, San Francisco, California, USA.
Anna K GreenDepartments of Clinical Genetics and Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Allan C SkanesSection of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, Western University, London, Ontario, Canada.
Anthony S TangSection of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, Western University, London, Ontario, Canada.
Martin J GardnerDivision of Cardiology, Department of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
Robert A HegeleRobarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada.
Toon Ab van VeenDepartment of Medical Physiology, Division of Heart and Lungs, University Medical Center, Utrecht, Utrecht University, Utrecht, Netherlands.
Arthur Am WildeAmsterdam University Medical Center, University of Amsterdam, Heart Centre, Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, Amsterdam, Netherlands.
Jeff S HealeyPopulation Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
Paul Ml JanssenDorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
Luisa MestroniCardiovascular Institute and Adult Medical Genetics Program, University of Colorado Denver, Aurora, Colorado, USA.
J Peter van TintelenDepartment of Genetics, University Medical Center Groningen, University of Groningen, Groningen, Netherlands.
Hugh CalkinsDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Daniel P JudgeDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
Thomas J HundDorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
Melvin M ScheinmanSection of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, UCSF, San Francisco, California, USA.
Peter J MohlerDorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
The Ohio State University Wexner Medical Center · USHospital for Sick Children · CAJohns Hopkins University · USWestern University · CAUniversity Medical Center Groningen · NLUniversity of Colorado Denver · USAmsterdam Neuroscience · NLLinköping University · SEUniversity Medical Center Utrecht · NLUniversity of California, San Francisco · USUniversity of Toronto · CACOMSATS University Islamabad · PKDalhousie University · CAOregon Health & Science University · USPopulation Health Research Institute · CAUniversidade de São Paulo · BRUniversity of Arizona · USUniversity of British Columbia · CAUniversity of Colorado Anschutz Medical Campus · USUniversity of Trieste · IT
Funding
Institute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1MBaylor-Johns Hopkins Center for Mendelian GeneticsUM1HG006542 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2016 to 2020
$14.5MDefining novel mechanisms for human arrhythmiaR35HL135754 · NHLBI · OHIO STATE UNIVERSITY · PI MOHLER, PETER J. · 2017 to 2023
$6.0MDefining novel mechanisms for regulation of atrial INa and arrhythmiasR01HL134824 · NHLBI · OHIO STATE UNIVERSITY · PI HUND, THOMAS JEFFREY, MOHLER, PETER J. · 2017 to 2020
$3.0MEHD proteins in cardiac membrane protein targeting and remodelingR01HL114383 · NHLBI · OHIO STATE UNIVERSITY · PI BOYDEN, PENELOPE ALTMAN, MOHLER, PETER J. · 2013 to 2016
$2.1MDefining the Impact of E-Cigarettes on Cardiac PathophysiologyR01HL139348 · NHLBI · OHIO STATE UNIVERSITY · PI WOLD, LOREN EUGENE · 2017 to 2020
$1.9MCaMKII-dependent regulation of cardiac excitabilityR01HL114893 · NHLBI · OHIO STATE UNIVERSITY · PI HUND, THOMAS JEFFREY · 2012 to 2016
$1.9MSpectrin-based regulation of cardiac remodeling and heart failureR01HL135096 · NHLBI · OHIO STATE UNIVERSITY · PI HUND, THOMAS JEFFREY · 2017 to 2020
$1.6MDefining new pathways for cardiac automaticityK99HL146969 · NHLBI · OHIO STATE UNIVERSITY · PI EL REFAEY, MONA · 2019 to 2020
$194kDefining the Role of Alpha II Spectrin in Cardiac Function and DiseaseF30HL137331 · NHLBI · OHIO STATE UNIVERSITY · PI LUBBERS, ELLEN · 2017 to 2020
$176kDefining Novel Mechanisms underlying Human Arrhythmogenic CardiomyopathyF30HL137325 · NHLBI · OHIO STATE UNIVERSITY · PI MURPHY, NATHANIEL PATRICK · 2017 to 2020
$163kNCATS NIH HHS UL1 TR001079NHGRI NIH HHS UM1 HG006542NHLBI NIH HHS F30 HL137325NHLBI NIH HHS F30 HL137331NHLBI NIH HHS K99 HL146969NHLBI NIH HHS R01 HL114383NHLBI NIH HHS R01 HL114893NHLBI NIH HHS R01 HL134824NHLBI NIH HHS R01 HL135096NHLBI NIH HHS R01 HL139348NHLBI NIH HHS R35 HL135754
Abstract
Arrhythmogenic cardiomyopathy (ACM) is an inherited arrhythmia syndrome characterized by severe structural and electrical cardiac phenotypes, including myocardial fibrofatty replacement and sudden cardiac death. Clinical management of ACM is largely palliative, owing to an absence of therapies that target its underlying pathophysiology, which stems partially from our limited insight into the condition. Following identification of deceased ACM probands possessing ANK2 rare variants and evidence of ankyrin-B loss of function on cardiac tissue analysis, an ANK2 mouse model was found to develop dramatic structural abnormalities reflective of human ACM, including biventricular dilation, reduced ejection fraction, cardiac fibrosis, and premature death. Desmosomal structure and function appeared preserved in diseased human and murine specimens in the presence of markedly abnormal β-catenin expression and patterning, leading to identification of a previously unknown interaction between ankyrin-B and β-catenin. A pharmacological activator of the WNT/β-catenin pathway, SB-216763, successfully prevented and partially reversed the murine ACM phenotypes. Our findings introduce what we believe to be a new pathway for ACM, a role of ankyrin-B in cardiac structure and signaling, a molecular link between ankyrin-B and β-catenin, and evidence for targeted activation of the WNT/β-catenin pathway as a potential treatment for this disease.
Indexed as
AnkyrinsArrhythmogenic Right Ventricular DysplasiaMyocardiumWnt Signaling PathwayAnimalsbeta CateninDisease Models, AnimalFemaleHumansIndolesMaleMaleimidesMiceMice, KnockoutANK2 protein, humanAnk2 protein, mouseAnkyrinsbeta CateninCTNNB1 protein, humanCTNNB1 protein, mouseIndolesMaleimidesSB 216763ArrhythmiasCardiologyCardiovascular diseaseCell BiologyGenetic diseases
Identifiers
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Registered trials
NCT06174220ClinicalTrials.gov
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.