Modeling Human Cardiac Hypertrophy in Stem Cell-Derived Cardiomyocytes
Ekaterina Ovchinnikova1, Martijn Hoes2, Kirill Ustyantsev3
1Department 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.
Insights
Human embryonic stem cell-derived cardiomyocytes (hESC-CMs) subjected to mechanical stretch mimic cardiac hypertrophy. This novel in vitro model advances understanding of mechanotransduction and disease mechanisms.
Area of Science:
- Cardiovascular Biology
- Stem Cell Research
- Molecular Cardiology
Background:
- Cardiac hypertrophy is a hallmark of cardiovascular diseases, but its mechanisms in humans remain unclear.
- A lack of human cardiomyocyte models hinders the study of cardiac hypertrophy.
- Understanding mechanotransduction is crucial for developing treatments.
Purpose of the Study:
- To establish and validate a human cardiomyocyte-based in vitro model for studying cardiac hypertrophy.
- To investigate the effects of mechanical stretch on human embryonic stem cell-derived cardiomyocytes (hESC-CMs).
- To explore the molecular underpinnings of cardiac hypertrophy using this new model.
Main Methods:
- Culturing and differentiating human embryonic stem cells into cardiomyocytes (hESC-CMs).
- Subjecting hESC-CMs to cyclic mechanical stretch to simulate in vivo conditions.
- Analyzing structural, functional, and gene expression changes in stretched hESC-CMs.
Main Results:
- hESC-CMs subjected to cyclic stretch exhibited key features of cardiac hypertrophy.
- Observed changes included structural remodeling, functional alterations, and modified gene expression.
- The model successfully recapitulated aspects of diseased myocardium.
Conclusions:
- Mechanical stretch of hESC-CMs provides a viable in vitro model for cardiac hypertrophy research.
- This model offers insights into mechanotransduction pathways involved in cardiac hypertrophy.
- It serves as a foundation for developing new pharmacological therapies and identifying biomarkers for cardiac dysfunction.
Abstract:
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.
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