ArticleJCI insight2019
Investigation of a dilated cardiomyopathy-associated variant in BAG3 using genome-edited iPSC-derived cardiomyocytes.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 46 citations in OpenAlex.
- Genetic vulnerability and dynamic mechanical stress synergistically drive sarcomere failure in human iPSC-derived cardiomyocytes.Materials today. Bio · 2026Article
- Cardiotoxicity induced by multiple myeloma therapies: mechanistic convergence across proteasome inhibitors, CAR-T, and bispecific antibodies.Blood cancer journal · 2026Review
- Genetic Architecture of N-Terminal Pro-B-Type Natriuretic Peptide in a Multiancestry Study Population.Circulation. Genomic and precision medicine · 2026Article
- Disrupted Sarcomere Reorganization of Cardiomyopathy-Prone Human iPSC-Derived Cardiomyocytes on a Dynamic Mechanical Substrate.Cellular and molecular bioengineering · 2025Article
- Induced Pluripotent Stem Cells in Cardiomyopathy: Advancing Disease Modeling, Therapeutic Development, and Regenerative Therapy.International journal of molecular sciences · 2025Review
- Integrating Prime Editing and Cellular Reprogramming as Novel Strategies for Genetic Cardiac Disease Modeling and Treatment.Current cardiology reports · 2024Review
- Current Status of Cardiac Regenerative Therapy Using Induced Pluripotent Stem Cells.International journal of molecular sciences · 2024Review
- Harnessing human genetics and stem cells for precision cardiovascular medicine.Cell genomics · 2024Review
- Dysregulated Autophagy and Sarcomere Dysfunction in Patients With Heart Failure With Co-Occurrence of P63A and P380SJournal of the American Heart Association · 2023Article
- Functional analysis of a common BAG3 allele associated with protection from heart failure.Nature cardiovascular research · 2023Article
- Bag3 Regulates Mitochondrial Function and the Inflammasome Through Canonical and Noncanonical Pathways in the Heart.JACC. Basic to translational science · 2023Article
- Transcriptome studies of inherited dilated cardiomyopathies.Mammalian genome : official journal of the International Mammalian Genome Society · 2023Review
- Functional genomics in stroke: current and future applications of iPSCs and gene editing to dissect the function of risk variants.BMC cardiovascular disorders · 2023Review
- Two Cases of Myofibrillar Myopathies: Genetic and Quality of Life Study.Muscles (Basel, Switzerland) · 2023Article
- Serine biosynthesis as a novel therapeutic target for dilated cardiomyopathy.European heart journal · 2022Article
- Machine learning and bioinformatics to identify 8 autophagy-related biomarkers and construct gene regulatory networks in dilated cardiomyopathy.Scientific reports · 2022Article
- CRISPR Modeling and Correction of Cardiovascular Disease.Circulation research · 2022Review
- Modeling Nonischemic Genetic Cardiomyopathies Using Induced Pluripotent Stem Cells.Current cardiology reports · 2022Review
- Cardiac calcium regulation in human induced pluripotent stem cell cardiomyocytes: Implications for disease modeling and maturation.Frontiers in cell and developmental biology · 2022Review
- The role of BAG3 in health and disease: A "Magic BAG of Tricks".Journal of cellular biochemistry · 2022Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Mutations in B cell lymphoma 2-associated athanogene 3 (BAG3) are recurrently associated with dilated cardiomyopathy (DCM) and muscular dystrophy. Using isogenic genome-edited human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs), we examined how a DCM-causing BAG3 mutation (R477H), as well as complete loss of BAG3 (KO), impacts myofibrillar organization and chaperone networks. Although unchanged at baseline, fiber length and alignment declined markedly in R477H and KO iPSC-CMs following proteasome inhibition. RNA sequencing revealed extensive baseline changes in chaperone- and stress response protein-encoding genes, and protein levels of key BAG3 binding partners were perturbed. Molecular dynamics simulations of the BAG3-HSC70 complex predicted a partial disengagement by the R477H mutation. In line with this, BAG3-R477H bound less HSC70 than BAG3-WT in coimmunoprecipitation assays. Finally, myofibrillar disarray triggered by proteasome inhibition in R477H cells was mitigated by overexpression of the stress response protein heat shock factor 1 (HSF1). These studies reveal the importance of BAG3 in coordinating protein quality control subsystem usage within the cardiomyocyte and suggest that augmenting HSF1 activity might be beneficial as a means to mitigate proteostatic stress in the context of BAG3-associated DCM.
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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.