ArticleJCI insight2017
Ectopic expression of Cdk8 induces eccentric hypertrophy and heart failure.
Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- Hi-Compass: a depth-aware deep learning framework for predicting cell-type-specific 3D genome organization from single-cell to spatial resolution.Nature communications · 2026Article
- Multitrait analyses identify genetic variants associated with aortic valve function and aortic stenosis risk.Nature genetics · 2026Article
- 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
- Med13 and Med13L: Critical redundant players in basal cardiac function and gene expression.Journal of molecular and cellular cardiology plus · 2025Article
- Mediator complex: update of key insights into transcriptional regulation of ancestral framework and its role in cardiovascular diseases.European journal of medical research · 2025Review
- Dietary Branched-Chain Amino Acids Modify Postinfarct Cardiac Remodeling and Function in the Murine Heart.Journal of the American Heart Association · 2025Article
- Dietary Branched Chain Amino Acids Modify Post-Infarct Cardiac Remodeling and Function in the Murine Heart.bioRxiv : the preprint server for biology · 2024Article
- ATF4-dependent increase in mitochondrial-endoplasmic reticulum tethering following OPA1 deletion in skeletal muscle.Journal of cellular physiology · 2024Article
- Neuronal nitric oxide synthase required for erythropoietin modulation of heart function in mice.Frontiers in physiology · 2024Article
- Blocking CDK7-Mediated NOTCH1-cMYC Signaling Attenuates Cancer Stem Cell Activity in Anaplastic Thyroid Cancer.Thyroid : official journal of the American Thyroid Association · 2022Article
- Association betweenCardiovascular diagnosis and therapy · 2021Article
- The Human Explanted Heart Program: A translational bridge for cardiovascular medicine.Biochimica et biophysica acta. Molecular basis of disease · 2021Review
- MicroRNA-9 facilitates hypoxia-induced injury and apoptosis in H9c2 cells via targeting CDK8.Journal of biosciences · 2021Article
- Article
- Epigenetic Reader BRD4 (Bromodomain-Containing Protein 4) Governs Nucleus-Encoded Mitochondrial Transcriptome to Regulate Cardiac Function.Circulation · 2020Article
- Stress-Induced Cyclin C Translocation Regulates Cardiac Mitochondrial Dynamics.Journal of the American Heart Association · 2020Article
- Heart disease in a mutant mouse model of spontaneous eosinophilic myocarditis maps to three loci.BMC genomics · 2019Article
- Targeting transcriptional machinery to inhibit enhancer-driven gene expression in heart failure.Heart failure reviews · 2019Review
- Endothelial and cardiomyocyte PI3Kβ divergently regulate cardiac remodelling in response to ischaemic injury.Cardiovascular research · 2019Article
- Regulation of cardiac transcription by thyroid hormone and Med13.Journal of molecular and cellular cardiology · 2019Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Widespread changes in cardiac gene expression occur during heart failure, yet the mechanisms responsible for coordinating these changes remain poorly understood. The Mediator complex represents a nodal point for modulating transcription by bridging chromatin-bound transcription factors with RNA polymerase II activity; it is reversibly regulated by its cyclin-dependent kinase 8 (Cdk8) kinase submodule. Here, we identified increased Cdk8 protein expression in human failing heart explants and determined the consequence of this increase in cardiac-specific Cdk8-expressing mice. Transgenic Cdk8 overexpression resulted in progressive dilated cardiomyopathy, heart failure, and premature lethality. Prior to functional decline, left ventricular cardiomyocytes were dramatically elongated, with disorganized transverse tubules and dysfunctional calcium handling. RNA sequencing results showed that myofilament gene isoforms not typically expressed in adult cardiomyocytes were enriched, while oxidative phosphorylation and fatty acid biosynthesis genes were downregulated. Interestingly, candidate upstream transcription factor expression levels and MAPK signaling pathways thought to determine cardiomyocyte size remained relatively unaffected, suggesting that Cdk8 functions within a novel growth regulatory pathway. Our findings show that manipulating cardiac gene expression through increased Cdk8 levels is detrimental to the heart by establishing a transcriptional program that induces pathological remodeling and eccentric hypertrophy culminating in heart failure.
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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.