Mice With Cardiac Overexpression of Peroxisome Proliferator–Activated Receptor γ Have Impaired Repolarization and Spontaneous Fatal Ventricular Arrhythmias

• DOI: 10.1161/circulationaha.111.056309
• Publication Date: 2011-11-30T02:46:56Z
• Authors: John P. Morrow; Alexander Katchman; Ni-Huiping Son; Chad M. Trent; Raffay Khan; Takayuki Shiomi; Haiyan Huang; Vaibhav Amin; Joshua M. Lader; Carolina Vasquez; Gregory E. Morley; Jeanine D'Armiento; Shunichi Homma; Ira J. Goldberg; Steven O. Marx
• Keywords: Sudden Death

Diabetes mellitus and obesity, which confer an increased risk of sudden cardiac death, are associated with cardiomyocyte lipid accumulation altered electric properties, manifested by prolongation the QRS duration QT interval. It is difficult to distinguish contribution from global metabolic defects incidence death abnormalities.In order study effects abnormalities on arrhythmias without complex systemic diabetes we studied transgenic mice cardiac-specific overexpression peroxisome proliferator-activated receptor γ 1 (PPARγ1) via α-myosin heavy-chain promoter. The PPARγ develop abnormal intracellular lipids die as young adults before any significant reduction in systolic function. Using implantable ECG telemeters, found that these have intervals spontaneous ventricular arrhythmias, including polymorphic tachycardia fibrillation. Isolated cardiomyocytes demonstrated prolonged action potential caused reduced expression function potassium channels responsible for repolarization. Short-term exposure pioglitazone, a agonist, had no effect mortality or rhythm WT but further exacerbated arrhythmic phenotype mice.Our findings support important link between activation, accumulation, ion channel remodeling, mortality.