Endothelin-1 influences mechanical properties and contractility of hiPSC derived cardiomyocytes resulting in diastolic dysfunction.

J Mol Cell Cardiol

Department for Internal Medicine B, Cardiology, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475 Greifswald, Germany; German Centre for Cardiovascular Research (DZHK), partner site Greifswald, Ferdinand-Sauerbruch-Straße, 17475 Greifswald, Germany. Electronic address:

Published: September 2024

A better understanding of the underlying pathomechanisms of diastolic dysfunction is crucial for the development of targeted therapeutic options with the aim to increase the patients' quality of life. In order to shed light on the processes involved, suitable models are required. Here, effects of endothelin-1 (ET-1) treatment on cardiomyocytes derived from human induced pluripotent stem cells (hiPSCs) were investigated. While it is well established, that ET-1 treatment induces hypertrophy in cardiomyocytes, resulting changes in cell mechanics and contractile behavior with focus on relaxation have not been examined before. Cardiomyocytes were treated with 10 nM of ET-1 for 24 h and 48 h, respectively. Hypertrophy was confirmed by real-time deformability cytometry (RT-DC) which was also used to assess the mechanical properties of cardiomyocytes. For investigation of the contractile behavior, 24 h phase contrast video microscopy was applied. To get a deeper insight into changes on the molecular biological level, gene expression analysis was performed using the NanoString nCounter® cardiovascular disease panel. Besides an increased cell size, ET-1 treated cardiomyocytes are stiffer and show an impaired relaxation. Gene expression patterns in ET-1 treated hiPSC derived cardiomyocytes showed that pathways associated with cardiovascular diseases, cardiac hypertrophy and extracellular matrix were upregulated while those associated with fatty acid metabolism were downregulated. We conclude that alterations in cardiomyocytes after ET-1 treatment go far beyond hypertrophy and represent a useful model for diastolic dysfunction.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yjmcc.2024.07.004DOI Listing

Publication Analysis

Top Keywords

diastolic dysfunction
12
et-1 treatment
12
mechanical properties
8
hipsc derived
8
cardiomyocytes
8
derived cardiomyocytes
8
contractile behavior
8
gene expression
8
et-1 treated
8
et-1
6

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!