Modeling Human Cardiac Hypertrophy in Stem Cell-Derived Cardiomyocytes.

Autor: Ovchinnikova E; Department of Cardiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, PO Box 30.001, Groningen, the Netherlands; European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Antonius Deusinglaan, 1, PO Box 196, Groningen, the Netherlands., Hoes M; Department of Cardiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, PO Box 30.001, Groningen, the Netherlands., Ustyantsev K; Laboratory of Molecular Genetic Systems, Institute of Cytology and Genetics, Novosibirsk, 630090, Russia., Bomer N; Department of Cardiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, PO Box 30.001, Groningen, the Netherlands., de Jong TV; European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Antonius Deusinglaan, 1, PO Box 196, Groningen, the Netherlands., van der Mei H; University of Groningen, University Medical Center Groningen, Biomedical Engineering Department, Groningen, 9713AV, the Netherlands., Berezikov E; European Research Institute for the Biology of Ageing, University of Groningen, University Medical Center Groningen, Antonius Deusinglaan, 1, PO Box 196, Groningen, the Netherlands. Electronic address: e.berezikov@umcg.nl., van der Meer P; Department of Cardiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, PO Box 30.001, Groningen, the Netherlands. Electronic address: p.van.der.meer@umcg.nl.
Jazyk: angličtina
Zdroj: Stem cell reports [Stem Cell Reports] 2018 Mar 13; Vol. 10 (3), pp. 794-807. Date of Electronic Publication: 2018 Feb 15.
DOI: 10.1016/j.stemcr.2018.01.016
Abstrakt: Cardiac hypertrophy accompanies many forms of cardiovascular diseases. The mechanisms behind the development and regulation of cardiac hypertrophy in the human setting are poorly understood, which can be partially attributed to the lack of a human cardiomyocyte-based preclinical test system recapitulating features of diseased myocardium. The objective of our study is to determine whether human embryonic stem cell-derived cardiomyocytes (hESC-CMs) subjected to mechanical stretch can be used as an adequate in vitro model for studying molecular mechanisms of cardiac hypertrophy. We show that hESC-CMs subjected to cyclic stretch, which mimics mechanical overload, exhibit essential features of a hypertrophic state on structural, functional, and gene expression levels. The presented hESC-CM stretch approach provides insight into molecular mechanisms behind mechanotransduction and cardiac hypertrophy and lays groundwork for the development of pharmacological approaches as well as for discovering potential circulating biomarkers of cardiac dysfunction.
(Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE