ArticleScience translational medicine2017
BET bromodomain inhibition suppresses innate inflammatory and profibrotic transcriptional networks in heart failure.
Article in Science translational medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 154 papers.
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Who cites it
154 citing papers in PubMed, 265 citations in OpenAlex.
- Apabetalone and hospitalization for heart failure in patients following an acute coronary syndrome: a prespecified analysis of the BETonMACE study.Cardiovascular diabetology · 2021Trial
- Cell Type-Specific Roles for BRD4 in Heart Failure.Current cardiology reports · 2026Review
- Next-generation molecular imaging of cardiac fibrosis.The international journal of cardiovascular imaging · 2026Review
- Heart-on-a-chip and vasculature-on-a-chip platforms as models of cardiovascular disease.Nature reviews. Cardiology · 2026Review
- The cardiac 4D nucleome: nuclear and chromatin dynamics across development, disease and ageing.Nature reviews. Cardiology · 2026Review
- The MEK inhibitor trametinib incurs mitochondrial injury and induces innate immune responses in the mouse heart.Science advances · 2026Article
- Histone Modifications in Cardiovascular Disease: Mechanisms and Therapeutic Opportunities.MedComm · 2026Review
- The impact of inflammation, neuromodulation, and gut microbiota on developing cardiac fibrosis and hypertension.Cardiovascular research · 2026Review
- Metabo-epigenetic circuits of heart failure: chromatin-modifying enzymes as determinants of metabolic plasticity.EMBO molecular medicine · 2026Review
- Cardio-Vascular Extracellular Matrix: The Unmet Enigma.International journal of molecular sciences · 2026Review
- The role of different types of programmed cell death in myocardial fibrosis: from mechanisms to therapeutics.Frontiers in cardiovascular medicine · 2026Review
- Epigenetic Regulatory Networks in Cardiac Fibrosis: Therapeutic Targets, Crosstalk, and Future Directions.Drug design, development and therapy · 2026Review
- Epigenetic regulation of cardiac physiology and pathophysiology: biological sex matters.The journal of cardiovascular aging · 2026Article
- Transcriptional signature of cardiac myocyte recovery in mice and human reveals persistent upregulation of epigenetic factors.Epigenetics · 2025Article
- Long-lasting metabolic impairment in the failing heart: epigenetic memories at play.Epigenetics · 2025Article
- Recharging the Powerhouse: Mitochondrial Dysfunction and Therapy in Cardiorenal Syndrome Type 4.Current heart failure reports · 2025Review
- Gαq-Stimulated Gene Expression Is Insensitive to Bromo Extra Terminal Domain Inhibitors in HEK 293 Cells.International journal of molecular sciences · 2025Article
- The MEK inhibitor trametinib incurs mitochondrial injury and induces innate immune responses in the mouse heart.bioRxiv : the preprint server for biology · 2025Article
- Established and Emerging Roles of Epigenetic Regulation in Diabetic Cardiomyopathy.Diabetes/metabolism research and reviews · 2025Review
- (+)-JQ-1 alleviates cardiac injury in myocardial infarction by inhibiting ferroptosis through the NAMPT/SIRT1 pathway.Cell death & disease · 2025Article
94 more citing papers are in PubMed but not listed here.
Corrections and comments
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- Erratum issued
Authors and funding
15 authors at 6 institutions in 2 countries.
Funding
Abstract
Despite current standard of care, the average 5-year mortality after an initial diagnosis of heart failure (HF) is about 40%, reflecting an urgent need for new therapeutic approaches. Previous studies demonstrated that the epigenetic reader protein bromodomain-containing protein 4 (BRD4), an emerging therapeutic target in cancer, functions as a critical coactivator of pathologic gene transactivation during cardiomyocyte hypertrophy. However, the therapeutic relevance of these findings to human disease remained unknown. We demonstrate that treatment with the BET bromodomain inhibitor JQ1 has therapeutic effects during severe, preestablished HF from prolonged pressure overload, as well as after a massive anterior myocardial infarction in mice. Furthermore, JQ1 potently blocks agonist-induced hypertrophy in human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Integrated transcriptomic analyses across animal models and human iPSC-CMs reveal that BET inhibition preferentially blocks transactivation of a common pathologic gene regulatory program that is robustly enriched for NFκB and TGF-β signaling networks, typified by innate inflammatory and profibrotic myocardial genes. As predicted by these specific transcriptional mechanisms, we found that JQ1 does not suppress physiological cardiac hypertrophy in a mouse swimming model. These findings establish that pharmacologically targeting innate inflammatory and profibrotic myocardial signaling networks at the level of chromatin is effective in animal models and human cardiomyocytes, providing the critical rationale for further development of BET inhibitors and other epigenomic medicines for HF.
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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.