ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Molecular and Cellular Pathology
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1627985
This article is part of the Research TopicElucidating the Role of Calcium Signaling in Cardiac DisordersView all articles
Altered endoplasmic reticulum calcium loading in human PLN R14del cardiomyopathy
Provisionally accepted
Willem Borbein
Lukas DahmlosUmber SaleemMarina Reinsch
Ingke BrarenThomas SchulzeBirgit Klampe
Friederike Cuello
Justus StenzigThomas Eschenhagen
Arne Hansen*- University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
The phospholamban (PLN) R14del genetic variant causes dilated cardiomyopathy. Previous studies suggest involvement of the ER stress response and impairment of ER-related signalling pathways such as autophagy. In this study, human induced pluripotent stem cell-derived cardiomyocytes from an unrelated control subject, PLN R14del patient and corresponding isogenic control were transduced with AAV6 encoding the endoplasmic reticulum calcium sensor CEPIAer. Indicator compounds for modulation of ER calcium homeostasis showed similar characteristic effects on CEPIAer fluorescence intensity in engineered heart tissues from all three cell lines, validating CEPIAer fluorescence intensity as a surrogate for ER calcium loading. Cytoplasmic calcium loading induced by high extracellular calcium concentration revealed subtle alterations in PLN R14del consistent with higher ER calcium loading. FACS analyses of dissociated cardiomyocytes confirmed higher ER calcium load. Taken together, this study provides evidence for altered ER calcium loading as a new disease mechanism in PLN R14del cardiomyopathy.
Keywords: Phospholamban R14del, Human Induced Pluripotent Stem Cells, Engineered heart tissue, Endoplasmic Reticulum, CEPIAer
Received: 13 May 2025; Accepted: 07 Jul 2025.
Copyright: © 2025 Borbein, Dahmlos, Saleem, Reinsch, Braren, Schulze, Klampe, Cuello, Stenzig, Eschenhagen and Hansen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Arne Hansen, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.