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Ambulatory ECG Recording in Mice
Published on: May 27, 2010
Accelerated cardiomyopathy in mice with overexpression of cardiac G(s)alpha and a missense mutation in the
Stefan E Hardt1, Yong-Jian Geng, Olivier Montagne
1Cardiovascular Research Institute, Department of Cell Biology, University of Medicine and Dentistry New Jersey, New Jersey Medical School, Newark, USA.
Circulation
|February 6, 2002
Summary
Familial hypertrophic cardiomyopathy worsened significantly in mice with both a myosin mutation and enhanced sympathetic drive. This synergistic effect, driven by elevated baseline function and sympathetic response, led to severe heart dysfunction and zero survival by 15 months.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Genetic Disease Models
Background:
- Familial hypertrophic cardiomyopathy (FHC) pathogenesis is not fully understood.
- Investigating the role of sympathetic drive in FHC progression is crucial.
Purpose of the Study:
- To determine how enhanced sympathetic drive affects cardiomyopathy induced by an alpha-myosin heavy chain mutation (Arg403-->Gln).
- To examine the synergistic effects of genetic mutation and sympathetic stimulation on cardiac function and survival.
Main Methods:
- Mated mice with an alpha-myosin heavy chain mutation (403) with mice overexpressing G(s)alpha to create a combined model (G(s)alpha x403).
- Assessed cardiac function using echocardiography and isolated cardiomyocyte contractility.
- Evaluated response to isoproterenol (sympathetic stimulant) in vivo.
- Monitored survival rates and performed histopathological analysis.
Main Results:
- G(s)alpha x403 mice exhibited elevated heart rate and enhanced left ventricular ejection fraction (LVEF) at 3 months.
- Cardiomyocytes from G(s)alpha x403 mice showed increased baseline contraction and normalized relaxation.
- While G(s)alpha x403 mice initially showed enhanced LVEF, it significantly depressed by 10 months.
- Severe myocyte hypertrophy, fibrosis, and 0% survival by 15 months were observed in G(s)alpha x403 mice.
Conclusions:
- The cardiomyopathy in G(s)alpha x403 mice results from a synergistic, not additive, interaction.
- Elevated baseline cardiac function combined with heightened sympathetic responsiveness drives the severe phenotype.
- This model highlights the critical interplay between genetic predisposition and autonomic nervous system activity in FHC.
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