Dexfenfluramine and Pergolide Cause Heart Valve Disease via Valve Metabolic Reprogramming and Ongoing Matrix Remodeling
| العنوان: | Dexfenfluramine and Pergolide Cause Heart Valve Disease via Valve Metabolic Reprogramming and Ongoing Matrix Remodeling |
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| المؤلفون: | Oury, Cécile, Maréchal, Patrick, Donis, Nathalie, Hulin, Alexia, Hego, Alexandre, Tridetti, Julien, Nguyen, Mai-Linh, Dulgheru, Raluca, Fillet, Marianne, Nchimi, Alain, Lancellotti, Patrizio |
| المصدر: | International Journal of Molecular Sciences, Vol 21, Iss 4003, p 4003 (2020) International Journal of Molecular Sciences |
| بيانات النشر: | MDPI AG, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Serotonin, Heart Valve Diseases, Administration, Oral, AMP-Activated Protein Kinases, p38 Mitogen-Activated Protein Kinases, Article, rabbit model, lcsh:Chemistry, Dexfenfluramine, Transforming Growth Factor beta, Animals, Cluster Analysis, Homeostasis, lcsh:QH301-705.5, Cell Proliferation, Sequence Analysis, RNA, Extracellular Matrix, Enzyme Activation, MicroRNAs, Gene Expression Regulation, lcsh:Biology (General), lcsh:QD1-999, valvular heart disease, Female, Rabbits, Tricuspid Valve, Transcriptome, serotonergic drugs, metabolism, Pergolide |
| الوصف: | Several clinical reports indicate that the use of amphetaminic anorectic drugs or ergot derivatives could cause valvular heart disease (VHD). We sought to investigate whether valvular lesions develop in response to long-term oral administration of these drugs and to identify drug-targeted biological processes that may lead to VHD. Treatment of New Zealand White rabbits with pergolide, dexfenfluramine, or high-dose serotonin for 16 weeks induced valvular alterations characterized by extracellular matrix remodeling. Transcriptome profiling of tricuspid valves using RNA sequencing revealed distinct patterns of differentially expressed genes (DEGs) that clustered according to the different treatments. Genes that were affected by the three treatments were functionally enriched for reduced cell metabolism processes. The two drugs yielded more changes in gene expression than serotonin and shared most of the DEGs. These DEGs were mostly enriched for decreased biosynthetic processes, increased cell-matrix interaction, and cell response to growth factors, including TGF-β, which was associated with p38 MAPK activation. Treatment with pergolide specifically affected genes involved in homeostasis, which was corroborated by the activation of the master regulator of cell energy homeostasis, AMPK-α, as well as decreased levels of metabolism-related miR-107. Thus, both pergolide and dexfenfluramine may cause VHD through valve metabolic reprogramming and matrix remodeling. |
| اللغة: | English |
| تدمد: | 1661-6596 1422-0067 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::73ff61117ed26a626e4561bb627e0715Test https://www.mdpi.com/1422-0067/21/11/4003Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.pmid.dedup....73ff61117ed26a626e4561bb627e0715 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16616596 14220067 |
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