Evidence map›Paper›PMID 41185038›Full record

ArticleStem cell research & therapy2025

Apremilast improves cardiomyocyte cohesion and arrhythmia in different models for arrhythmogenic cardiomyopathy.

Konstanze Stangner, Orsela Dervishi, Janina Kuhnert, Carl Wendt, Soumyata Pathak, Maria Shoykhet, Silvana Olivares-Florez, Sina Moztarzadeh, Jens Opsteen, Ni Luh Cathrin Suniasih Wohlfarth and 8 more

Abstract read
In one paragraph

Article in Stem cell research & therapy, 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

18 authors.

Konstanze Stangner *Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, Ludwig-Maximilians-University (LMU) Munich, Pettenkoferstrasse 11, 80336, Munich, Germany.
Orsela Dervishi *Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, Ludwig-Maximilians-University (LMU) Munich, Pettenkoferstrasse 11, 80336, Munich, Germany.
Janina KuhnertChair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, Ludwig-Maximilians-University (LMU) Munich, Pettenkoferstrasse 11, 80336, Munich, Germany.
Carl WendtChair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, Ludwig-Maximilians-University (LMU) Munich, Pettenkoferstrasse 11, 80336, Munich, Germany.
Soumyata PathakChair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, Ludwig-Maximilians-University (LMU) Munich, Pettenkoferstrasse 11, 80336, Munich, Germany.
Maria ShoykhetChair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, Ludwig-Maximilians-University (LMU) Munich, Pettenkoferstrasse 11, 80336, Munich, Germany.
Silvana Olivares-FlorezChair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, Ludwig-Maximilians-University (LMU) Munich, Pettenkoferstrasse 11, 80336, Munich, Germany.
Sina MoztarzadehChair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, Ludwig-Maximilians-University (LMU) Munich, Pettenkoferstrasse 11, 80336, Munich, Germany.
Jens OpsteenFaculty of Medicine and University Hospital Cologne, Center for Physiology and Pathophysiology, Institute for Neurophysiology, University of Cologne, Robert Koch Str. 39, 50931, Cologne, Germany.
Ni Luh Cathrin Suniasih WohlfarthFaculty of Medicine and University Hospital Cologne, Center for Physiology and Pathophysiology, Institute for Neurophysiology, University of Cologne, Robert Koch Str. 39, 50931, Cologne, Germany.
Ruth BillerARVC- Selbsthilfe e.V., patient association, Munich, Germany.
Elisabeth GrafInstitute of Human Genetics, School of Medicine, Technical University of Munich, Munich, Germany.
Dominik S WestphalInstitute of Human Genetics, School of Medicine, Technical University of Munich, Munich, Germany.
Tatjana WilliamsComprehensive Heart Failure Center, Department of Medicine I, University Hospital Würzburg, Würzburg, Germany.
Brenda GerullComprehensive Heart Failure Center, Department of Medicine I, University Hospital Würzburg, Würzburg, Germany.
Tomo Šarić *Faculty of Medicine and University Hospital Cologne, Center for Physiology and Pathophysiology, Institute for Neurophysiology, University of Cologne, Robert Koch Str. 39, 50931, Cologne, Germany. tomo.saric@uni-koeln.de.
Sunil Yeruva *Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, Ludwig-Maximilians-University (LMU) Munich, Pettenkoferstrasse 11, 80336, Munich, Germany. sunil.yeruva@med.uni-muenchen.de.
Jens Waschke *Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, Ludwig-Maximilians-University (LMU) Munich, Pettenkoferstrasse 11, 80336, Munich, Germany. jens.waschke@med.uni-muenchen.de.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundArrhythmogenic cardiomyopathy (ACM) is a genetically inherited desmosome heart disease leading to life-threatening arrhythmias and sudden cardiac death. Currently, ACM treatment paradigms are merely symptom targeting. Recently, apremilast was shown to stabilize keratinocyte adhesion in the desmosomal disease pemphigus vulgaris. Therefore, this study investigated whether apremilast can be a therapeutic option for ACM.

methodsHuman induced pluripotent stem cells from a healthy control (hiPSC) and an ACM index patient (ACM-hiPSC) carrying a heterozygous desmoplakin (DSP) gene mutation (c.2854G > T, p.Glu952Ter), confirmed by whole exome sequencing (WES), were established. Cyclic-AMP ELISA, dissociation assay, immunostaining, and Western blotting analyses were performed in human iPSC-derived cardiomyocytes (hiPSC-CMs), murine HL-1 cardiomyocytes, and cardiac slices derived from wild-type (WT) mice, plakoglobin (PG, Jup) knockout (Jup

resultsACM-hiPSC derived cardiomyocytes (ACM-hiPSC-CMs) revealed a significant loss of cohesion, which was rescued by apremilast. Further, treatment with apremilast strengthened basal cardiomyocyte cohesion in HL-1 cells and WT murine cardiac slices, paralleled by phosphorylation of PG at Serine 665 in human and murine models. In HL-1 cells, apremilast in addition activated ERK1/2, inhibition of which abolished apremilast-enhanced cardiomyocyte cohesion. Further, dissociation assays in slice cultures from JUP-S665A and Jup

conclusionsApremilast improves loss of cardiomyocyte cohesion, enhances localization of DSG2, and reduces arrhythmia in human and/or murine models of ACM ex vivo and in vitro, providing a novel treatment strategy for ACM by preserving desmosome function.

Indexed as

Arrhythmias, CardiacArrhythmogenic Right Ventricular DysplasiaMyocytes, CardiacThalidomideAnimalsDesmoplakinsDisease Models, Animalgamma CateninHumansInduced Pluripotent Stem CellsMiceMice, KnockoutapremilastDesmoplakinsgamma CateninThalidomideApremilastArrhythmiaArrhythmogenic cardiomyopathyDesmoplakin and desmoglein 2

Identifiers

PMID41185038
PMCPMC12584335

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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.