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Updated: May 27, 2026
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Viral Transgene Expression in Rodent Hearts and the Assessment of Cardiac Arrhythmia Risk
Published on: July 27, 2022
Mice with cardiac overexpression of peroxisome proliferator-activated receptor γ have impaired repolarization and
John P Morrow1, Alexander Katchman, Ni-Huiping Son
1Columbia University, Division of Cardiology, PH 10-203, 622 W.168th St, New York, NY, USA. jpm46@columbia.edu
Circulation
|November 30, 2011
Summary
Peroxisome proliferator-activated receptor gamma 1 (PPARγ1) activation in the heart causes lipid buildup, leading to arrhythmias and sudden cardiac death in mice. This highlights a link between PPARγ, lipid accumulation, and cardiac mortality.
Area of Science:
- Cardiology
- Metabolic Disorders
- Molecular Biology
Background:
- Diabetes and obesity increase sudden cardiac death risk due to cardiomyocyte lipid accumulation and altered cardiac electrical properties.
- Distinguishing the specific role of cardiomyocyte lipid accumulation versus systemic metabolic defects in cardiac events is challenging.
Purpose of the Study:
- To investigate the impact of metabolic abnormalities on cardiac arrhythmias independent of systemic diabetes or obesity.
- To elucidate the role of cardiac-specific peroxisome proliferator-activated receptor gamma 1 (PPARγ1) in lipid accumulation and arrhythmogenesis.
Main Methods:
- Generated transgenic mice with cardiac-specific PPARγ1 overexpression using the α-myosin heavy-chain promoter.
- Utilized implantable ECG telemetry to monitor cardiac electrical activity and arrhythmias.
- Examined isolated cardiomyocytes to assess action potential duration and potassium channel function.
Main Results:
- PPARγ1 transgenic mice exhibited intracellular lipid accumulation, premature death, prolonged QRS and QT intervals, and spontaneous ventricular arrhythmias.
- Cardiomyocytes showed prolonged action potential duration due to reduced potassium channel expression and function.
- PPARγ agonist pioglitazone worsened arrhythmias and increased mortality in transgenic mice, but not in wild-type mice.
Conclusions:
- Findings establish a significant association between PPARγ activation, cardiomyocyte lipid accumulation, and ion channel remodeling.
- This pathway contributes to an increased risk of cardiac mortality.
