ArticleJournal of molecular and cellular cardiology2014
Phenotypic screen quantifying differential regulation of cardiac myocyte hypertrophy identifies CITED4 regulation of myocyte elongation.
Article in Journal of molecular and cellular cardiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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Who cites it
33 citing papers in PubMed, 48 citations in OpenAlex.
- Exercise-induced cardiac hypertrophy: cellular and molecular mechanisms of cardiac adaptation following physical activity.Postepy w kardiologii interwencyjnej = Advances in interventional cardiology · 2026Review
- Single-cell dynamics reveal a stress-induced decision between hypertrophy and apoptosis in neonatal rat cardiomyocytes.Journal of molecular and cellular cardiology plus · 2025Article
- CITED Proteins in Cardiac Development and Lifelong Heart Function.Journal of personalized medicine · 2025Review
- Systems analysis reveals neuregulin-1 control of cardiomyocyte size and shape mediated by distinct PI3K and p38 pathways.bioRxiv : the preprint server for biology · 2025Article
- Mesencephalic Astrocyte-Derived Neurotrophic Factor Binds BAX to Preserve Mitochondrial Homeostasis and Energy Metabolism for Relieving Myocardial Hypertrophy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Molecular Mediators of the Cardiac Benefits of Exercise.Circulation research · 2025Review
- Identifying metabolic adaptations characteristic of cardiotoxicity using paired transcriptomics and metabolomics data integrated with a computational model of heart metabolism.PLoS computational biology · 2024Article
- Exercise Promotes Tissue Regeneration: Mechanisms Involved and Therapeutic Scope.Sports medicine - open · 2023Review
- A Kinase Interacting Protein 1 (AKIP1) promotes cardiomyocyte elongation and physiological cardiac remodelling.Scientific reports · 2023Article
- Molecular mechanisms of exercise contributing to tissue regeneration.Signal transduction and targeted therapy · 2022Review
- Exercise-induced CITED4 expression is necessary for regional remodeling of cardiac microstructural tissue helicity.Communications biology · 2022Article
- Exercise: a molecular tool to boost muscle growth and mitochondrial performance in heart failure?European journal of heart failure · 2022Review
- C-MORE: A high-content single-cell morphology recognition methodology for liquid biopsies toward personalized cardiovascular medicine.Cell reports. Medicine · 2021Article
- Integrated Quantitative Phosphoproteomics and Cell-based Functional Screening Reveals Specific Pathological Cardiac Hypertrophy-related Phosphorylation Sites.Molecules and cells · 2021Article
- Targets identified from exercised heart: killing multiple birds with one stone.NPJ Regenerative medicine · 2021Review
- Network Analysis Reveals a Distinct Axis of Macrophage Activation in Response to Conflicting Inflammatory Cues.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- Context-specific network modeling identifies new crosstalk in β-adrenergic cardiac hypertrophy.PLoS computational biology · 2020Article
- CITED4 Protects Against Adverse Remodeling in Response to Physiological and Pathological Stress.Circulation research · 2020Article
- Protective transcriptional mechanisms in cardiomyocytes and cardiac fibroblasts.Journal of molecular and cellular cardiology · 2019Review
- Quantitative systems models illuminate arrhythmia mechanisms in heart failure: Role of the NaWiley interdisciplinary reviews. Systems biology and medicine · 2019Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Cardiac hypertrophy is controlled by a highly connected signaling network with many effectors of cardiac myocyte size. Quantification of the contribution of individual pathways to specific changes in shape and transcript abundance is needed to better understand hypertrophy signaling and to improve heart failure therapies. We stimulated cardiac myocytes with 15 hypertrophic agonists and quantitatively characterized differential regulation of 5 shape features using high-throughput microscopy and transcript levels of 12 genes using qPCR. Transcripts measured were associated with phenotypes including fibrosis, cell death, contractility, proliferation, angiogenesis, inflammation, and the fetal cardiac gene program. While hypertrophy pathways are highly connected, the agonist screen revealed distinct hypertrophy phenotypic signatures for the 15 receptor agonists. We then used k-means clustering of inputs and outputs to identify a network map linking input modules to output modules. Five modules were identified within inputs and outputs with many maladaptive outputs grouping together in one module: Bax, C/EBPβ, Serca2a, TNFα, and CTGF. Subsequently, we identified mechanisms underlying two correlations revealed in the agonist screen: correlation between regulators of fibrosis and cell death signaling (CTGF and Bax mRNA) caused by AngII; and myocyte proliferation (CITED4 mRNA) and elongation caused by Nrg1. Follow-up experiments revealed positive regulation of Bax mRNA level by CTGF and an incoherent feedforward loop linking Nrg1, CITED4 and elongation. With this agonist screen, we identified the most influential inputs in the cardiac hypertrophy signaling network for a variety of features related to pathological and protective hypertrophy signaling and shared regulation among cardiac myocyte phenotypes.
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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.