Dexfenfluramine and Pergolide Cause Heart Valve Disease via Valve Metabolic Reprogramming and Ongoing Matrix Remodeling
Abstract
:1. Introduction
2. Results
2.1. Oral Serotonin, Pergolide, and Dexfenfluramine Cause Valvular Lesions with Distinct Histological Features
2.2. RNA Profiling Identifies Gene Expression Patterns of Drug-Induced Valvular Alterations
2.3. Gene Ontology Analyses Depict Enrichment of Distinct Biological Processes Leading to Valve Remodeling
3. Discussion
4. Materials and Methods
4.1. Rabbits
4.2. Measurements of Pergolide and Dexfenfluramine in Rabbit Plasma
4.3. Histology and Immunohistochemistry
4.4. RNA Isolation
4.5. RNA Sequencing, Data Processing, and Analysis
4.6. Gene Enrichment Analysis
4.7. Real-Time Quantitative PCR
4.8. Protein Extraction and Western Blotting
4.9. Statistics
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
AMPK DEG | AMP-activated protein kinase Differentially expressed gene |
ECM VHD VIC | Extracellular matrix Valvular heart disease Valvular interstitial cell |
TGF-β | Transforming growth factor-β |
MAPK | Mitogen-activated protein kinase |
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Oury, C.; Maréchal, P.; Donis, N.; Hulin, A.; Hego, A.; Tridetti, J.; Nguyen, M.-L.; Dulgheru, R.; Fillet, M.; Nchimi, A.; et al. Dexfenfluramine and Pergolide Cause Heart Valve Disease via Valve Metabolic Reprogramming and Ongoing Matrix Remodeling. Int. J. Mol. Sci. 2020, 21, 4003. https://doi.org/10.3390/ijms21114003
Oury C, Maréchal P, Donis N, Hulin A, Hego A, Tridetti J, Nguyen M-L, Dulgheru R, Fillet M, Nchimi A, et al. Dexfenfluramine and Pergolide Cause Heart Valve Disease via Valve Metabolic Reprogramming and Ongoing Matrix Remodeling. International Journal of Molecular Sciences. 2020; 21(11):4003. https://doi.org/10.3390/ijms21114003
Chicago/Turabian StyleOury, Cécile, Patrick Maréchal, Nathalie Donis, Alexia Hulin, Alexandre Hego, Julien Tridetti, Mai-Linh Nguyen, Raluca Dulgheru, Marianne Fillet, Alain Nchimi, and et al. 2020. "Dexfenfluramine and Pergolide Cause Heart Valve Disease via Valve Metabolic Reprogramming and Ongoing Matrix Remodeling" International Journal of Molecular Sciences 21, no. 11: 4003. https://doi.org/10.3390/ijms21114003