Evidence map›Paper›PMID 41145823›Full record

ArticleCommunications biology2025

Modelling arrhythmogenic cardiomyopathy fattyfibro pathology with PKP2-deficient epicardial cells derived from human iPSCs.

Sadia L Falana, Sobhi G Kazmouz, Jessika B Iwanski, Sailu Sarvagalla, Blaire E Bas, Elizabeth Juneman, Talal Moukabary, Ning Ma, Rebekah L Gundry, Leili Rohani and 5 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Communications biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Sadia L FalanaDepartment of Cellular and Molecular Medicine, The University of Arizona, Tucson, AZ, USA.
Sobhi G KazmouzDepartment of Cellular and Molecular Medicine, The University of Arizona, Tucson, AZ, USA.
Jessika B IwanskiDepartment of Internal Medicine, UT Southwestern Medical Center, Dallas, TX, USA.
Sailu SarvagallaDepartment of Cellular and Molecular Medicine, The University of Arizona, Tucson, AZ, USA.
Blaire E BasDepartment of Cellular and Molecular Medicine, The University of Arizona, Tucson, AZ, USA.
Elizabeth JunemanMolecular Cardiovascular Research Program, The University of Arizona, Tucson, AZ, USA.
Talal MoukabaryMolecular Cardiovascular Research Program, The University of Arizona, Tucson, AZ, USA.ORCID http://orcid.org/0000-0001-6557-6404
Ning MaSchool of Basic Medical Sciences, Guangzhou Laboratory, Guangzhou Medical University, Guangzhou, Guangdong Province, China.ORCID http://orcid.org/0000-0002-1775-2992
Rebekah L GundryCardiOmics Program, Center for Heart and Vascular Research, and Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, USA.ORCID http://orcid.org/0000-0002-9263-833X
Leili RohaniDivision of Cardiology, University of British Columbia, Vancouver, BC, Canada.
Paul HansonDivision of Cardiology, University of British Columbia, Vancouver, BC, Canada.
Zachary LaksmanDivision of Cardiology, University of British Columbia, Vancouver, BC, Canada.
Cynthia A JamesDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.ORCID http://orcid.org/0000-0001-8040-4600
Hugh CalkinDivision of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Jared M ChurkoDepartment of Cellular and Molecular Medicine, The University of Arizona, Tucson, AZ, USA. jchurko@arizona.edu.ORCID http://orcid.org/0000-0003-3537-9834

Funding

Harnessing Glycoproteomics and Glycomics to Understand Cardiac Biology and DiseaseR35HL155460 · NHLBI · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI Rebekah L. Gundry · 2021 to 2026
$4.6M
NHLBI NIH HHS R35 HL155460
6 · The paper itself

Abstract

Arrhythmogenic cardiomyopathy (ACM) is an inherited heart disease marked by progressive fattyfibro replacement of the ventricular myocardium, life-threatening arrhythmias, and sudden cardiac death. To dissect epicardial contributions to ACM pathogenesis, we generated iPSC lines from patients carrying plakophilin 2 (PKP2) 1849C > T or PKP2 2013delC mutations, their CRISPR/Cas9-corrected isogenic controls, and a PKP2 knockout line. Epicardial cells (hPSC-EPCs) differentiated from mutant and knockout backgrounds exhibit enhanced epithelial-to-mesenchymal transition characteristics, increased lipid accumulation, and a pronounced fibrotic phenotype. RNA-seq performed on ACM hPSC-EPCs reveals dysregulation of Wnt, interferon, and Rho GTPase signaling, including an upregulation of insulin growth factor 2 (IGF2) and a key adipogenic transcription factor, CEBPA. Subsequent treatment of control and PKP2KO hPSC-EPCs with recombinant IGF2 enhances CEBPA expression, suggesting that insulin growth factor signaling contributes to ACM fattyfibro remodeling.

Indexed as

Arrhythmogenic Right Ventricular DysplasiaInduced Pluripotent Stem CellsPericardiumPlakophilinsHumansInsulin-Like Growth Factor IIInsulin-Like Growth Factor IIPKP2 protein, humanPlakophilins

Identifiers

PMID41145823
PMCPMC12559194

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

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.