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Updated: Dec 27, 2025
In Vitro Assessment of Cardiac Function Using Skinned Cardiomyocytes
Published on: June 22, 2020
New insights provided by myofibril mechanics in inherited cardiomyopathies
Ying-Hsi Lin1,2, Jonathan Yap3, Chrishan J A Ramachandra1,2
1National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore.
Insights
Investigating single myofibril function offers insights into inherited cardiomyopathies like hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM). This approach helps understand how sarcomeric mutations cause disease and identify potential therapies.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Genetics
Background:
- Cardiomyopathies are cardiac disorders affecting contraction and relaxation, leading to heart failure and sudden death.
- Inherited cardiomyopathies are linked to mutations in sarcomeric protein genes.
- Genotype-phenotype correlations are complex due to genetic and environmental factors.
Purpose of the Study:
- To review myofibril function techniques for studying cardiomyopathies.
- To discuss alterations in myofibril mechanics caused by sarcomeric mutations.
- To explore therapeutic potential for sarcomeric cardiomyopathies.
Main Methods:
- Utilizing isolated single myofibril function techniques.
- Analyzing myofibril bundles from human and animal hearts.
- Employing cultured adult cardiomyocytes and induced pluripotent stem cell-derived cardiomyocytes.
- Establishing a multi-level, cross-species research platform.
Main Results:
- Sarcomeric genetic mutations are associated with inherited hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and restrictive cardiomyopathy (RCM).
- Myofibril function techniques reveal specific mechanical alterations linked to these mutations.
- This research platform facilitates dissection of sarcomeric function in various cardiomyopathy models.
Conclusions:
- Single myofibril function analysis is crucial for understanding the molecular basis of inherited cardiomyopathies.
- Identifying specific myofibril mechanical changes can aid in diagnosing and treating sarcomeric cardiomyopathies.
- This approach holds promise for future therapeutic target identification.
Abstract:
Cardiomyopathies represent a heterogeneous group of cardiac disorders that perturb cardiac contraction and/or relaxation, and can result in arrhythmias, heart failure, and sudden cardiac death. Based on morphological and functional differences, cardiomyopathies have been classified into hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and restrictive cardiomyopathy (RCM). It has been well documented that mutations in genes encoding sarcomeric proteins are associated with the onset of inherited cardiomyopathies. However, correlating patient genotype to the clinical phenotype has been challenging because of the complex genetic backgrounds, environmental influences, and lifestyles of individuals. Thus, "scaling down" the focus to the basic contractile unit of heart muscle using isolated single myofibril function techniques is of great importance and may be used to understand the molecular basis of disease-causing sarcomeric mutations. Single myofibril bundles harvested from diseased human or experimental animal hearts, as well as cultured adult cardiomyocytes or human cardiomyocytes derived from induced pluripotent stem cells, can be used, thereby providing an ideal multi-level, cross-species platform to dissect sarcomeric function in cardiomyopathies. Here, we will review the myofibril function technique, and discuss alterations in myofibril mechanics, which are known to occur in sarcomeric genetic mutations linked to inherited HCM, DCM, and RCM, and describe the therapeutic potential for future target identification.
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