ArticleInternational journal of molecular sciences2019
The BET Bromodomain Inhibitor I-BET-151 Induces Structural and Functional Alterations of the Heart Mitochondria in Healthy Male Mice and Rats.
Article in International journal of molecular sciences, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- A randomized study of the safety and pharmacokinetics of GSK3358699, a mononuclear myeloid-targeted bromodomain and extra-terminal domain inhibitor.British journal of clinical pharmacology · 2022Trial
- Precision Medicine for Pulmonary Vascular Disease: The Future Is Now (2023 Grover Conference Series).Pulmonary circulation · 2025Article
- Unlocking the secrets of aging: Epigenetic reader BRD4 as the target to combatting aging-related diseases.Journal of advanced research · 2024Review
- Targeting BRD4: Potential therapeutic strategy for head and neck squamous cell carcinoma (Review).Oncology reports · 2024Article
- Novel Techniques, Biomarkers and Molecular Targets to Address Cardiometabolic Diseases.Journal of clinical medicine · 2024Review
- Lactate Utilization Enables Metabolic Escape to Confer Resistance to BET Inhibition in Acute Myeloid Leukemia.Cancer research · 2024Article
- Superenhancers as master gene regulators and novel therapeutic targets in brain tumors.Experimental & molecular medicine · 2023Review
- The Emerging Role of Super-enhancers as Therapeutic Targets in The Digestive System Tumors.International journal of biological sciences · 2023Review
- Epigenetic Reader BRD4 (Bromodomain-Containing Protein 4) Governs Nucleus-Encoded Mitochondrial Transcriptome to Regulate Cardiac Function.Circulation · 2020Article
- Epigenetic Targets for Oligonucleotide Therapies of Pulmonary Arterial Hypertension.International journal of molecular sciences · 2020Review
- Targeting complexes of super-enhancers is a promising strategy for cancer therapy.Oncology letters · 2020Review
- Brd4-p300 inhibition downregulates Nox4 and accelerates lung fibrosis resolution in aged mice.JCI insight · 2020Article
- Article
- Reply to Piquereau and Perros and to Pullamsetti and de Jesus Perez.American journal of respiratory and critical care medicine · 2019Article
- BET Bromodomain Inhibitors and Pulmonary Arterial Hypertension: Take Care of the Heart.American journal of respiratory and critical care medicine · 2019Article
- EpiHope for the Treatment of Pulmonary Arterial Hypertension: Selective versus Nonselective BET Inhibition.American journal of respiratory and critical care medicine · 2019Article
- Bromodomain and Extraterminal Proteins as Novel Epigenetic Targets for Renal Diseases.Frontiers in pharmacology · 2019Review
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
The bromodomain and extra-terminal domain family inhibitors (BETi) are a promising new class of anticancer agents. Since numerous anticancer drugs have been correlated to cardiomyopathy, and since BETi can affect non-cancerous tissues, we aimed to investigate in healthy animals any ultrastructural BETi-induced alterations of the heart as compared to skeletal muscle. Male Wistar rats were either treated during 3 weeks with I-BET-151 (2 or 10 mg/kg/day) (W3) or treated for 3 weeks then allowed to recover for another 3 weeks (W6) (3-weeks drug washout). Male C57Bl/6J mice were only treated during 5 days (50 mg/kg/day). We demonstrated the occurrence of ultrastructural alterations and progressive destruction of cardiomyocyte mitochondria after I-BET-151 exposure. Those mitochondrial alterations were cardiac muscle-specific, since the skeletal muscles of exposed animals were similar in ultrastructure presentation to the non-exposed animals. I-BET-151 decreased the respiration rate of heart mitochondria in a dose-dependent manner. At the higher dose, it also decreased mitochondrial mass, as evidenced by reduced right ventricular citrate synthase content. I-BET-151 reduced the right and left ventricular fractional shortening. The concomitant decrease in the velocity-time-integral in both the aorta and the pulmonary artery is also suggestive of an impaired heart function. The possible context-dependent cardiac side effects of these drugs have to be appreciated. Future studies should focus on the basic mechanisms of potential cardiovascular toxicities induced by BETi and strategies to minimize these unexpected complications.
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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.