Article (Scientific journals)
Dexfenfluramine and Pergolide Cause Heart Valve Disease via Valve Metabolic Reprogramming and Ongoing Matrix Remodeling.
Oury, Cécile; MARECHAL, Patrick; Donis, Nathalie et al.
2020In International Journal of Molecular Sciences, 21 (11)
Peer Reviewed verified by ORBi
 

Files


Full Text
ijms-21-04003.pdf
Publisher postprint (5.82 MB)
Download

All documents in ORBi are protected by a user license.

Send to



Details



Keywords :
metabolism; rabbit model; serotonergic drugs; valvular heart disease
Abstract :
[en] 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.
Disciplines :
Cardiovascular & respiratory systems
Author, co-author :
Oury, Cécile  ;  Université de Liège - ULiège > Cardiovascular Sciences-Cardiology
MARECHAL, Patrick ;  Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Cardiologie multidisciplinaire et prévention
Donis, Nathalie ;  Université de Liège - ULiège > Cardiovascular Sciences-Cardiology
Hulin, Alexia 
Hego, Alexandre 
TRIDETTI, Julien 
Nguyen, Mai-Linh
DULGHERU, Raluca Elena 
Fillet, Marianne  ;  Université de Liège - ULiège > Département de pharmacie > Analyse des médicaments
Nchimi Longang, Alain ;  Université de Liège - ULiège > Département des sciences cliniques > Cardiologie - Pathologie spéciale et réhabilitation
Lancellotti, Patrizio  ;  Université de Liège - ULiège > Département des sciences cliniques > Cardiologie - Pathologie spéciale et réhabilitation
Language :
English
Title :
Dexfenfluramine and Pergolide Cause Heart Valve Disease via Valve Metabolic Reprogramming and Ongoing Matrix Remodeling.
Publication date :
2020
Journal title :
International Journal of Molecular Sciences
ISSN :
1661-6596
eISSN :
1422-0067
Publisher :
Multidisciplinary Digital Publishing Institute (MDPI), Switzerland
Volume :
21
Issue :
11
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 03 July 2020

Statistics


Number of views
119 (15 by ULiège)
Number of downloads
69 (11 by ULiège)

Scopus citations®
 
2
Scopus citations®
without self-citations
2
OpenCitations
 
1

Bibliography


Similar publications



Contact ORBi