ArticleCardiovascular research2020
Chronic intermittent tachypacing by an optogenetic approach induces arrhythmia vulnerability in human engineered heart tissue.
Article in Cardiovascular research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 47 citations in OpenAlex.
- Optogenetic tachypacing facilitates burst-induced arrhythmia in stem cell-derived human atrial engineered heart tissue.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2026Article
- Advanced in vitro cardiac models for drug evaluation: integration of organoids, engineered tissues, and microphysiological systems.Microsystems & nanoengineering · 2026Review
- Modeling heart rhythm using human engineered heart tissues.Nature protocols · 2026Review
- Arrhythmogenic Risk in iPSC-Derived Cardiomyocytes: Current Limitations and Therapeutic Perspectives.Medicina (Kaunas, Lithuania) · 2025Review
- High Rate Triggers Increased Atrial Release of BMP10, A Biomarker for Atrial Fibrillation and Stroke, and BMP10 Affects Ventricular Cardiomyocytes.Circulation. Arrhythmia and electrophysiology · 2025Article
- Review
- Tachycardia-induced metabolic rewiring as a driver of contractile dysfunction.Nature biomedical engineering · 2024Article
- Optical mapping and optogenetics in cardiac electrophysiology research and therapy: a state-of-the-art review.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2024Review
- A comprehensive review on 3D tissue models: Biofabrication technologies and preclinical applications.Biomaterials · 2024Review
- Atrial fibrillation-associated electrical remodelling in human induced pluripotent stem cell-derived atrial cardiomyocytes: a novel pathway for antiarrhythmic therapy development.Cardiovascular research · 2023Article
- Modulating cardiac physiology in engineered heart tissue with the bidirectional optogenetic tool BiPOLES.Pflugers Archiv : European journal of physiology · 2023Article
- Recent advances in regulating the proliferation or maturation of human-induced pluripotent stem cell-derived cardiomyocytes.Stem cell research & therapy · 2023Review
- Towards Improved HumanBiomedicines · 2023Review
- Contractile Force of Transplanted Cardiomyocytes Actively Supports Heart Function After Injury.Circulation · 2022Article
- Opportunities and challenges in cardiac tissue engineering from an analysis of two decades of advances.Nature biomedical engineering · 2022Review
- Human Organoids and Organs-on-Chips for Addressing COVID-19 Challenges.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Review
- Optogenetic Control of Human Induced Pluripotent Stem Cell-Derived Cardiac Tissue Models.Journal of the American Heart Association · 2022Article
- From engineered heart tissue to cardiac organoid.Theranostics · 2022Review
- Human Engineered Heart Tissue Models for Disease Modeling and Drug Discovery.Frontiers in cell and developmental biology · 2022Review
- Engineered models of the human heart: Directions and challenges.Stem cell reports · 2021Review
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsChronic tachypacing is commonly used in animals to induce cardiac dysfunction and to study mechanisms of heart failure and arrhythmogenesis. Human induced pluripotent stem cells (hiPSC) may replace animal models to overcome species differences and ethical problems. Here, 3D engineered heart tissue (EHT) was used to investigate the effect of chronic tachypacing on hiPSC-cardiomyocytes (hiPSC-CMs). METHODS AND
resultsTo avoid cell toxicity by electrical pacing, we developed an optogenetic approach. EHTs were transduced with lentivirus expressing channelrhodopsin-2 (H134R) and stimulated by 15 s bursts of blue light pulses (0.3 mW/mm2, 30 ms, 3 Hz) separated by 15 s without pacing for 3 weeks. Chronic optical tachypacing did not affect contractile peak force, but induced faster contraction kinetics, shorter action potentials, and shorter effective refractory periods. This electrical remodelling increased vulnerability to tachycardia episodes upon electrical burst pacing. Lower calsequestrin 2 protein levels, faster diastolic depolarization (DD) and efficacy of JTV-519 (46% at 1 µmol/L) to terminate tachycardia indicate alterations of Ca2+ handling being part of the underlying mechanism. However, other antiarrhythmic compounds like flecainide (69% at 1 µmol/L) and E-4031 (100% at 1 µmol/L) were also effective, but not ivabradine (1 µmol/L) or SEA0400 (10 µmol/L).
conclusionWe demonstrated a high vulnerability to tachycardia of optically tachypaced hiPSC-CMs in EHT and the effective termination by ryanodine receptor stabilization, sodium or hERG potassium channel inhibition. This new model might serve as a preclinical tool to test antiarrhythmic drugs increasing the insight in treating ventricular tachycardia.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.