ArticleCirculation2011
Mice with cardiac overexpression of peroxisome proliferator-activated receptor γ have impaired repolarization and spontaneous fatal ventricular arrhythmias.
Article in Circulation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 66 citations in OpenAlex.
- Cardiac Lipid Metabolism: Cells, Metabolites, and Rhythms.Circulation research · 2026Review
- Review
- Immune cells and arrhythmias.Cardiovascular research · 2025Review
- The Effect of Obesity on Repolarization and Other ECG Parameters.Journal of clinical medicine · 2024Article
- Cardiac GR Mediates the Diurnal Rhythm in Ventricular Arrhythmia Susceptibility.Circulation research · 2024Article
- Obesity-induced activation of NADPH oxidase 2 prolongs cardiac repolarization via inhibiting K+ currents.PloS one · 2024Article
- Localized cardiomyocyte lipid accumulation is associated with slowed epicardial conduction in rats.The Journal of general physiology · 2023Article
- Cadherin-11-Interleukin-6 Signaling between Cardiac Fibroblast and Cardiomyocyte Promotes Ventricular Remodeling in a Mouse Pressure Overload-Induced Heart Failure Model.International journal of molecular sciences · 2023Article
- Adipogenic Signaling Promotes Arrhythmia Substrates before Structural Abnormalities in TMEM43 ARVC.Journal of personalized medicine · 2022Article
- The PPARγ pathway determines electrophysiological remodelling and arrhythmia risks in DSC2 arrhythmogenic cardiomyopathy.Clinical and translational medicine · 2022Article
- CaPflugers Archiv : European journal of physiology · 2022Review
- The mitochondrial calcium uniporter promotes arrhythmias caused by high-fat diet.Scientific reports · 2021Article
- The Glitazars Paradox: Cardiotoxicity of the Metabolically Beneficial Dual PPARα and PPARγ Activation.Journal of cardiovascular pharmacology · 2020Review
- Mechanisms of Chronic Metabolic Stress in Arrhythmias.Antioxidants (Basel, Switzerland) · 2020Review
- PKCδ causes sepsis-induced cardiomyopathy by inducing mitochondrial dysfunction.American journal of physiology. Heart and circulatory physiology · 2020Article
- Shensong Yangxin Protects Against Metabolic Syndrome-Induced Ventricular Arrhythmias by Inhibiting Electrical Remodeling.Frontiers in pharmacology · 2020Article
- The effect of MD1 on potassium and L-type calcium current of cardiomyocytes from high-fat diet mice.Channels (Austin, Tex.) · 2020Article
- Cardiac overexpression of perilipin 2 induces atrial steatosis, connexin 43 remodeling, and atrial fibrillation in aged mice.American journal of physiology. Endocrinology and metabolism · 2019Article
- Increased arrhythmia susceptibility in type 2 diabetic mice related to dysregulation of ventricular sympathetic innervation.American journal of physiology. Heart and circulatory physiology · 2019Article
- Dietary Saturated Fat Promotes Arrhythmia by Activating NOX2 (NADPH Oxidase 2).Circulation. Arrhythmia and electrophysiology · 2019Article
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
backgroundDiabetes mellitus and obesity, which confer an increased risk of sudden cardiac death, are associated with cardiomyocyte lipid accumulation and altered cardiac electric properties, manifested by prolongation of the QRS duration and QT interval. It is difficult to distinguish the contribution of cardiomyocyte lipid accumulation from the contribution of global metabolic defects to the increased incidence of sudden death and electric abnormalities. METHODS AND
resultsIn order to study the effects of metabolic abnormalities on arrhythmias without the complex systemic effects of diabetes mellitus and obesity, we studied transgenic mice with cardiac-specific overexpression of peroxisome proliferator-activated receptor γ 1 (PPARγ1) via the cardiac α-myosin heavy-chain promoter. The PPARγ transgenic mice develop abnormal accumulation of intracellular lipids and die as young adults before any significant reduction in systolic function. Using implantable ECG telemeters, we found that these mice have prolongation of the QRS and QT intervals and spontaneous ventricular arrhythmias, including polymorphic ventricular tachycardia and ventricular fibrillation. Isolated cardiomyocytes demonstrated prolonged action potential duration caused by reduced expression and function of the potassium channels responsible for repolarization. Short-term exposure to pioglitazone, a PPARγ agonist, had no effect on mortality or rhythm in WT mice but further exacerbated the arrhythmic phenotype and increased the mortality in the PPARγ transgenic mice.
conclusionsOur findings support an important link between PPARγ activation, cardiomyocyte lipid accumulation, ion channel remodeling, and increased cardiac mortality.
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