ArticleCell stem cell2015
Epigenetic Regulation of Phosphodiesterases 2A and 3A Underlies Compromised β-Adrenergic Signaling in an iPSC Model of Dilated Cardiomyopathy.
Article in Cell stem cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers, 2 of them syntheses that pooled it.
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Who cites it
130 citing papers in PubMed, 2 syntheses or guidelines pooled it, 174 citations in OpenAlex.
- Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes as an in vitro model in toxicology: strengths and weaknesses for hazard identification and risk characterization.Expert opinion on drug metabolism & toxicology · 2021Pooled it
- Cardiomyopathy phenotypes in human-induced pluripotent stem cell-derived cardiomyocytes-a systematic review.Pflugers Archiv : European journal of physiology · 2019Pooled it
- Evidence for a role of adverse sarcomere signaling in atrial fibrillation induction.Journal of molecular and cellular cardiology plus · 2026Review
- Troponin: biology, molecular mechanisms, and multidimensional clinical applications.Molecular biomedicine · 2026Review
- Evaluating and comparing the signalling and functional landscape of hiPSC-CMs derived from patients with dilated cardiomyopathy.npj biomedical innovations · 2026Article
- Targeting intracellular cholesterol imbalance rescues sarcomere-ER contact site signaling and ER remodeling in dilated cardiomyopathy.Signal transduction and targeted therapy · 2026Article
- A humanized engineered heart tissue platform for cardiotoxicity assessment.Stem cell reports · 2026Article
- ROS-induced degradation of hERG potassium channels contributes to aripiprazole-induced prolongation of the QTc interval.Acta pharmacologica Sinica · 2026Article
- Pediatric dilated cardiomyopathy caused by TNNT2-R151W mutation: Modeling and rescue in patient-derived induced pluripotent stem cells and engineered heart tissue.Bioengineering & translational medicine · 2026Article
- Humanized hiPSC Platforms for I/R Injury: Advancing Toward Precision Cardioprotection.Cardiovascular therapeutics · 2026Review
- Decoding long COVID-associated cardiovascular dysfunction: Mechanisms, models, and new approach methodologies.Journal of molecular and cellular cardiology · 2025Review
- Cardiomyocyte Nuclear Pleomorphism in a Mouse Model of Inherited Hypertrophic Cardiomyopathy.Journal of cardiovascular development and disease · 2025Article
- Dynamic proteome profiling of differentiating human embryonic stem cells towards cardiomyocytes.Scientific reports · 2025Article
- Review
- Novel Metabolites Genetically Linked to Salt Sensitivity of Blood Pressure: Evidence from mGWAS in Chinese Population.International journal of molecular sciences · 2025Article
- Vinculin haploinsufficiency impairs integrin-mediated costamere remodeling on stiffer microenvironments.Journal of molecular and cellular cardiology · 2025Article
- Advancements in techniques for human iPSC-derived cardiomyocytes maturation: mechanical and electrical stimulation approaches.Biophysical reviews · 2025Review
- Inhibition of GRK2-PDE4D Axis Suppresses Fibroblast-Like Synoviocytes Hyperplasia and Alleviates Experimental Arthritis.International journal of biological sciences · 2025Article
- Dilated cardiomyopathy-associated skeletal muscle actin (ACTA1) mutation R256H disrupts actin structure and function and causes cardiomyocyte hypocontractility.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Focus on cardiac troponin complex: From gene expression to cardiomyopathy.Genes & diseases · 2024Review
70 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
Abstract
β-adrenergic signaling pathways mediate key aspects of cardiac function. Its dysregulation is associated with a range of cardiac diseases, including dilated cardiomyopathy (DCM). Previously, we established an iPSC model of familial DCM from patients with a mutation in TNNT2, a sarcomeric protein. Here, we found that the β-adrenergic agonist isoproterenol induced mature β-adrenergic signaling in iPSC-derived cardiomyocytes (iPSC-CMs) but that this pathway was blunted in DCM iPSC-CMs. Although expression levels of several β-adrenergic signaling components were unaltered between control and DCM iPSC-CMs, we found that phosphodiesterases (PDEs) 2A and PDE3A were upregulated in DCM iPSC-CMs and that PDE2A was also upregulated in DCM patient tissue. We further discovered increased nuclear localization of mutant TNNT2 and epigenetic modifications of PDE genes in both DCM iPSC-CMs and patient tissue. Notably, pharmacologic inhibition of PDE2A and PDE3A restored cAMP levels and ameliorated the impaired β-adrenergic signaling of DCM iPSC-CMs, suggesting therapeutic potential.
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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.