ArticleEBioMedicine2015
BET Bromodomain Blockade Mitigates Intimal Hyperplasia in Rat Carotid Arteries.
Article in EBioMedicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 65 citations in OpenAlex.
- BET inhibitors in cardiovascular diseases: from atherosclerosis to heart failure.Pharmacological reports : PR · 2026Review
- (+)-JQ-1 alleviates cardiac injury in myocardial infarction by inhibiting ferroptosis through the NAMPT/SIRT1 pathway.Cell death & disease · 2025Article
- Nano-based perivascular intervention sustains a nine-month long-term suppression of intimal hyperplasia in vein grafts.Bioactive materials · 2025Article
- Vascular restenosis following paclitaxel-coated balloon therapy is attributable to NLRP3 activation and LIN9 upregulation.Journal of translational medicine · 2024Article
- Unlocking the secrets of aging: Epigenetic reader BRD4 as the target to combatting aging-related diseases.Journal of advanced research · 2024Review
- FAM222A, Part of the BET-Regulated Basal Endothelial Transcriptome, Is a Novel Determinant of Endothelial Biology and Angiogenesis-Brief Report.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- The role of 6-phosphogluconate dehydrogenase in vascular smooth muscle cell phenotypic switching and angioplasty-induced intimal hyperplasia.JVS-vascular science · 2024Article
- Neointima abating and endothelium preserving - An adventitia-localized nanoformulation to inhibit the epigenetic writer DOT1L.Biomaterials · 2023Article
- Epigenetic Reader Bromodomain-Containing Protein 4 in Aging-Related Vascular Pathologies and Diseases: Molecular Basis, Functional Relevance, and Clinical Potential.Biomolecules · 2023Review
- Article
- Gene-repressing epigenetic reader EED unexpectedly enhances cyclinD1 gene activation.Molecular therapy. Nucleic acids · 2023Article
- miR579-3p is an inhibitory modulator of neointimal hyperplasia and transcription factors c-MYB and KLF4.Cell death discovery · 2023Article
- R132H IDH1 sensitizes glioma to the antiproliferative and cytotoxic effects of BET inhibition.Journal of cancer research and clinical oncology · 2022Article
- SREBP1 regulatesMolecular therapy. Nucleic acids · 2022Article
- Angioplasty induces epigenomic remodeling in injured arteries.Life science alliance · 2022Article
- Computational repurposing of therapeutic small molecules from cancer to pulmonary hypertension.Science advances · 2021Article
- Biomimetic, ROS-detonable nanoclusters - A multimodal nanoplatform for anti-restenotic therapy.Journal of controlled release : official journal of the Controlled Release Society · 2021Article
- A hierarchical and collaborative BRD4/CEBPD partnership governs vascular smooth muscle cell inflammation.Molecular therapy. Methods & clinical development · 2021Article
- Targeting the epigenome in in-stent restenosis: from mechanisms to therapy.Molecular therapy. Nucleic acids · 2021Review
- A Role for Polo-Like Kinase 4 in Vascular Fibroblast Cell-Type Transition.JACC. Basic to translational science · 2021Article
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7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundIntimal hyperplasia is a common cause of many vasculopathies. There has been a recent surge of interest in the bromo and extra-terminal (BET) epigenetic "readers" including BRD4 since the serendipitous discovery of JQ1(+), an inhibitor specific to the seemingly undruggable BET bromodomains. The role of the BET family in the development of intimal hyperplasia is not known.
methodsWe investigated the effect of BET inhibition on intimal hyperplasia using a rat balloon angioplasty model.
resultsWhile BRD4 was dramatically up-regulated in the rat and human hyperplastic neointima, blocking BET bromodomains with JQ1(+) diminished neointima in rats. Knocking down BRD4 with siRNA, or treatment with JQ1(+) but not the inactive enantiomer JQ1(-), abrogated platelet-derived growth factor (PDGF-BB)-stimulated proliferation and migration of primary rat aortic smooth muscle cells. This inhibitory effect of JQ1(+) was reproducible in primary human aortic smooth muscle cells. In human aortic endothelial cells, JQ1(+) prevented cytokine-induced apoptosis and impairment of cell migration. Furthermore, either BRD4 siRNA or JQ1(+) but not JQ1(-), substantially down-regulated PDGF receptor-α which, in JQ1(+)-treated arteries versus vehicle control, was also reduced.
conclusionsBlocking BET bromodomains mitigates neointima formation, suggesting an epigenetic approach for effective prevention of intimal hyperplasia and associated vascular diseases.
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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.