ArticleJCI insight2022
Mutant ANP induces mitochondrial and ion channel remodeling in a human iPSC-derived atrial fibrillation model.
Article in JCI insight, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- Reconstructing AF-associated atrial fibrosis: Patient-specific iPSC models, fit-for-purpose atrial microphysiological systems, and nanomedicine.Materials today. Bio · 2026Review
- Gene-gene interactions between a LMNA variant and common polymorphisms drive early-onset atrial fibrillation.Nature communications · 2026Article
- Human iPSCs: atrial versus ventricular cardiomyocytes and their functional and pharmacological differences.Biochemical Society transactions · 2026Review
- A titin missense variant drives atrial electrical remodeling and is associated with atrial fibrillation.eLife · 2026Article
- Ionic Disorders in Persistent Atrial Fibrillation: Therapeutic Targeting by Plant-Derived Bioactive Compounds.Cardiology research and practice · 2026Review
- A titin missense variant drives atrial electrical remodeling and is associated with atrial fibrillation.medRxiv : the preprint server for health sciences · 2025Article
- The role of iPSC research for insight into inherited arrhythmia conditions.Heart rhythm · 2025Review
- Cardiac corin and atrial natriuretic peptide regulate liver glycogen metabolism and glucose homeostasis.Cardiovascular diabetology · 2024Article
- Identification of the optimal reference genes for atrial fibrillation model established by iPSC-derived atrial myocytes.BMC genomics · 2024Article
- Modulation of NOX2 causes obesity-mediated atrial fibrillation.The Journal of clinical investigation · 2024Article
- Transient titin-dependent ventricular defects during development lead to adult atrial arrhythmia and impaired contractility.iScience · 2024Article
- Genetics and Pharmacogenetics of Atrial Fibrillation: A Mechanistic Perspective.JACC. Basic to translational science · 2024Review
- Human induced pluripotent stem cell-derived atrial cardiomyocytes recapitulate contribution of the slowly activating delayed rectifier currents IKs to repolarization in the human atrium.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 · 2024Article
- Engineered cocultures of iPSC-derived atrial cardiomyocytes and atrial fibroblasts for modeling atrial fibrillation.Science advances · 2024Article
- Article
- Development of a robust induced pluripotent stem cell atrial cardiomyocyte differentiation protocol to model atrial arrhythmia.Stem cell research & therapy · 2023Article
- Natriuretic Peptides: It Is Time for Guided Therapeutic Strategies Based on Their Molecular Mechanisms.International journal of molecular sciences · 2023Review
- PITX2 gain-of-function mutation associated with atrial fibrillation alters mitochondrial activity in human iPSC atrial-like cardiomyocytes.Frontiers in physiology · 2023Article
- The role of macrophage ion channels in the progression of atherosclerosis.Frontiers in immunology · 2023Review
- Article
Corrections and comments
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Authors and funding
17 authors at 2 institutions in 2 countries.
Funding
Abstract
Human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) can model heritable arrhythmias to personalize therapies for individual patients. Although atrial fibrillation (AF) is a leading cause of cardiovascular morbidity and mortality, current platforms to generate iPSC-atrial (a) CMs are inadequate for modeling AF. We applied a combinatorial engineering approach, which integrated multiple physiological cues, including metabolic conditioning and electrical stimulation, to generate mature iPSC-aCMs. Using the patient's own atrial tissue as a gold standard benchmark, we assessed the electrophysiological, structural, metabolic, and molecular maturation of iPSC-aCMs. Unbiased transcriptomic analysis and inference from gene regulatory networks identified key gene expression pathways and transcription factors mediating atrial development and maturation. Only mature iPSC-aCMs generated from patients with heritable AF carrying the non-ion channel gene (NPPA) mutation showed enhanced expression and function of a cardiac potassium channel and revealed mitochondrial electron transport chain dysfunction. Collectively, we propose that ion channel remodeling in conjunction with metabolic defects created an electrophysiological substrate for AF. Overall, our electro-metabolic approach generated mature human iPSC-aCMs that unmasked the underlying mechanism of the first non-ion channel gene, NPPA, that causes AF. Our maturation approach will allow for the investigation of the molecular underpinnings of heritable AF and the development of personalized therapies.
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Registered trials
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.