ArticleCell stem cell2022
Uncompensated mitochondrial oxidative stress underlies heart failure in an iPSC-derived model of congenital heart disease.
Article in Cell stem cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 79 citations in OpenAlex.
- Hypoplastic Left Heart Syndrome Cardiomyocytes Exhibit Intrinsic Stress Vulnerabilities and Augmented Stress Responses in vitro.Stem cell reviews and reports · 2026Article
- ELABELA Targets Mitochondria to Modulate Heart Development.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Mitochondrial dysfunction underlies cardiac contractility and growth defects in a zebrafish model ofbioRxiv : the preprint server for biology · 2026Article
- Inhibition of Cyclophilin D Rescues Cardiac Function and Bioenergetic Defects Caused by Neonatal Hypoxia.JACC. Basic to translational science · 2026Article
- Mosaic: Single-Cell Atlas of Stress.Cells · 2026Review
- Endoplasmic reticulum stress in disease pathogenesis: its implications for therapy.Signal transduction and targeted therapy · 2026Review
- Single-cell omics uncovers novel pathological mechanisms and therapeutic targets for congenital heart diseases: insights from integrated intercellular communication analysis.Stem cell research & therapy · 2026Review
- Ventricular assist device unloading reverses microvascular senescence in single ventricle disease.Nature cardiovascular research · 2026Article
- Microvascular senescence in single ventricle disease.Nature cardiovascular research · 2026Article
- Early multi-omic signatures and machine learning models predict cardiomyocyte differentiation efficiency and enable robust hPSC differentiation to cardiomyocytes.bioRxiv : the preprint server for biology · 2026Article
- Comprehensive perturbation of transcription factors in human cardiomyocytes reveals the regulatory architecture of congenital heart disease.bioRxiv : the preprint server for biology · 2026Article
- Advancing Congenital Heart Defect Treatments: Synergistic Approaches with Stem Cells and Functional Scaffolds.Stem cell reviews and reports · 2026Review
- Spatiotemporal Atlas of Heart Development Reveals Blood-Flow-Dependent Cellular, Structural, Metabolic, and Spatial Remodeling.bioRxiv : the preprint server for biology · 2025Article
- Article
- Mitochondria-Targeted Antioxidants Prevent Tachypacing-Induced Contractile Dysfunction in In Vitro Cardiomyocyte and In VivoAntioxidants (Basel, Switzerland) · 2025Article
- EnterotoxigenicBiology · 2025Article
- AI662270/GRP94 axis couples the unfolded protein response to mitochondrial dynamics during acute myocardial infarction.JCI insight · 2025Article
- Review
- Earthing effects on mitochondrial function: ATP production and ROS generation.FEBS open bio · 2025Article
- Dysfunctional Electron Transport Chain Assembly in COXPD8.Journal of cardiovascular development and disease · 2025Article
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Authors and funding
23 authors at 7 institutions in 3 countries.
Funding
Abstract
Hypoplastic left heart syndrome (HLHS) is a severe congenital heart disease with 30% mortality from heart failure (HF) in the first year of life, but the cause of early HF remains unknown. Induced pluripotent stem-cell-derived cardiomyocytes (iPSC-CM) from patients with HLHS showed that early HF is associated with increased apoptosis, mitochondrial respiration defects, and redox stress from abnormal mitochondrial permeability transition pore (mPTP) opening and failed antioxidant response. In contrast, iPSC-CM from patients without early HF showed normal respiration with elevated antioxidant response. Single-cell transcriptomics confirmed that early HF is associated with mitochondrial dysfunction accompanied with endoplasmic reticulum (ER) stress. These findings indicate that uncompensated oxidative stress underlies early HF in HLHS. Importantly, mitochondrial respiration defects, oxidative stress, and apoptosis were rescued by treatment with sildenafil to inhibit mPTP opening or TUDCA to suppress ER stress. Together these findings point to the potential use of patient iPSC-CM for modeling clinical heart failure and the development of therapeutics.
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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.