ArticleHeart rhythm2016
Mitochondrial oxidative stress during cardiac lipid overload causes intracellular calcium leak and arrhythmia.
Article in Heart rhythm, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 53 citations in OpenAlex.
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- Cardiac Cell Remodeling in Obesity and Diabetes.Handbook of experimental pharmacology · 2026Review
- The Adipokine Hypothesis of Heart Failure With a Preserved Ejection Fraction: A Novel Framework to Explain Pathogenesis and Guide Treatment.Journal of the American College of Cardiology · 2025Review
- Semaglutide normalizes increased cardiomyocyte calcium transients in a rat model of high fat diet-induced obesity.ESC heart failure · 2025Article
- The triglyceride-glucose index, ventricular arrhythmias and major cardiovascular events in patients at high risk of sudden cardiac death.Cardiovascular diabetology · 2024Observational
- Methionine sulfoxide reductase B2 protects against cardiac complications in diabetes mellitus.Diabetology & metabolic syndrome · 2024Article
- Modeling drug-induced mitochondrial toxicity with human primary cardiomyocytes.Science China. Life sciences · 2024Article
- Role of Mitochondrial ROS for Calcium Alternans in Atrial Myocytes.Biomolecules · 2024Article
- New drug discovery of cardiac anti-arrhythmic drugs: insights in animal models.Scientific reports · 2023Article
- Sexual dimorphism in bidirectional SR-mitochondria crosstalk in ventricular cardiomyocytes.Basic research in cardiology · 2023Article
- Diabetes-induced chronic heart failure is due to defects in calcium transporting and regulatory contractile proteins: cellular and molecular evidence.Heart failure reviews · 2023Review
- The interplay of inflammation, exosomes and CaCardiovascular diabetology · 2023Review
- Oxidative Stress as a Reliable Biomarker of Carotid Plaque Instability: A Pilot Study.Antioxidants (Basel, Switzerland) · 2023Article
- The Role of Mitochondrial Abnormalities in Diabetic Cardiomyopathy.International journal of molecular sciences · 2022Review
- Animal Models to Study Cardiac Arrhythmias.Circulation research · 2022Review
- ER stress and calcium-dependent arrhythmias.Frontiers in physiology · 2022Review
- The Role of Oxidative Stress in Acute Ischemic Stroke-Related Thrombosis.Oxidative medicine and cellular longevity · 2022Review
- MCU overexpression evokes disparate dose-dependent effects on mito-ROS and spontaneous CaAmerican journal of physiology. Heart and circulatory physiology · 2021Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundDiabetes and obesity are associated with an increased risk of arrhythmia and sudden cardiac death. Abnormal lipid accumulation is observed in cardiomyocytes of obese and diabetic patients, which may contribute to arrhythmia, but the mechanisms are poorly understood. A transgenic mouse model of cardiac lipid overload, the peroxisome proliferator-activated receptor-γ (PPARg) cardiac overexpression mouse, has long QT and increased ventricular ectopy.
objectiveThe purpose of this study was to evaluate the hypothesis that the increase in ventricular ectopy during cardiac lipid overload is caused by abnormalities in calcium handling due to increased mitochondrial oxidative stress.
methodsVentricular myocytes were isolated from adult mouse hearts to record sparks and calcium transients. Mice were implanted with heart rhythm monitors for in vivo recordings.
resultsPPARg cardiomyocytes have more frequent triggered activity and increased sparks compared to control. Sparks and triggered activity are reduced by mitotempo, a mitochondrial-targeted antioxidant. This is explained by a significant increase in oxidation of RyR2. Calcium transients are increased in amplitude, and sarcoplasmic reticulum (SR) calcium stores are increased in PPARg cardiomyocytes. Computer modeling of the cardiac action potential demonstrates that long QT contributes to increased SR calcium. Mitotempo decreased ventricular ectopy in vivo.
conclusionDuring cardiac lipid overload, mitochondrial oxidative stress causes increased SR calcium leak by oxidizing RyR2 channels. This promotes ventricular ectopy, which is significantly reduced in vivo by a mitochondrial-targeted antioxidant. These results suggest a potential role for mitochondrial-targeted antioxidants in preventing arrhythmia and sudden cardiac death in obese and diabetic patients.
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