Related Experiment Video
Updated: Aug 14, 2026
An Approach to Study Shape-Dependent Transcriptomics at a Single Cell Level
Published on: November 2, 2020
Somatic events modify hypertrophic cardiomyopathy pathology and link hypertrophy to arrhythmia
Cordula M Wolf1, Ivan P G Moskowitz, Scott Arno
1Department of Cardiology, Children's Hospital, Boston, MA 02115, USA.
Insights
Genetic mutations in sarcomere proteins cause hypertrophic cardiomyopathy (HCM). In HCM mice, cardiac hypertrophy, not fibrosis or myocyte disarray, correlated with arrhythmia susceptibility, suggesting a shared pathway linking hypertrophy and arrhythmias.
Area of Science:
- Cardiology
- Genetics
- Molecular Biology
Background:
- Sarcomere protein gene mutations lead to hypertrophic cardiomyopathy (HCM).
- HCM is characterized by myocyte disarray and cardiac fibrosis, presumed triggers for arrhythmias and sudden cardiac death.
- Human studies are confounded by genetic heterogeneity and lifestyle factors.
Purpose of the Study:
- To investigate the relationship between HCM pathology and cardiac arrhythmias.
- To assess the roles of myocyte disarray, cardiac fibrosis, and hypertrophy in arrhythmia susceptibility.
- To elucidate the underlying mechanisms linking sarcomere mutations to HCM and arrhythmias.
Main Methods:
- Studied cardiac electrophysiology, hypertrophy, and histopathology in engineered HCM mice (both outbred and inbred).
- Assessed ex vivo signal conduction properties and in vivo electrophysiologically stimulated arrhythmias.
- Correlated histopathological findings (myocyte disarray, fibrosis) and ventricular hypertrophy with arrhythmia susceptibility.
Main Results:
- HCM mice exhibited variable arrhythmia susceptibility, ventricular hypertrophy, and histopathology.
- Neither the extent nor location of myocyte disarray or cardiac fibrosis correlated with arrhythmia properties in inbred HCM mice.
- Ventricular hypertrophy significantly correlated with increased arrhythmia susceptibility.
Conclusions:
- Distinct somatic events contribute to variable HCM pathology.
- Cardiac hypertrophy, rather than fibrosis or myocyte disarray, is associated with increased arrhythmic risk in HCM.
- A shared pathway initiated by sarcomere gene mutations likely links cardiac hypertrophy and arrhythmias in HCM.
Abstract:
Sarcomere protein gene mutations cause hypertrophic cardiomyopathy (HCM), a disease with distinctive histopathology and increased susceptibility to cardiac arrhythmias and risk for sudden death. Myocyte disarray (disorganized cell-cell contact) and cardiac fibrosis, the prototypic but protean features of HCM histopathology, are presumed triggers for ventricular arrhythmias that precipitate sudden death events. To assess relationships between arrhythmias and HCM pathology without confounding human variables, such as genetic heterogeneity of disease-causing mutations, background genotypes, and lifestyles, we studied cardiac electrophysiology, hypertrophy, and histopathology in mice engineered to carry an HCM mutation. Both genetically outbred and inbred HCM mice had variable susceptibility to arrhythmias, differences in ventricular hypertrophy, and variable amounts and distribution of histopathology. Among inbred HCM mice, neither the extent nor location of myocyte disarray or cardiac fibrosis correlated with ex vivo signal conduction properties or in vivo electrophysiologically stimulated arrhythmias. In contrast, the amount of ventricular hypertrophy was significantly associated with increased arrhythmia susceptibility. These data demonstrate that distinct somatic events contribute to variable HCM pathology and that cardiac hypertrophy, more than fibrosis or disarray, correlates with arrhythmic risk. We suggest that a shared pathway triggered by sarcomere gene mutations links cardiac hypertrophy and arrhythmias in HCM.
Related Concept Videos
01:29Cardiomyopathy III: Hypertrophic Cardiomyopathy
01:26Cellular Adaptation II: Hypertrophy
01:25Cardiomyopathy I: Introduction and Classification
01:29Heart Failure II: Pathophysiology
01:29Cardiomyopathy V: Interprofessional Care
01:29Pathophysiology of Cardiac Performance