RNAseq analysis of heart tissue from mice treated with atenolol and isoproterenol reveals a reciprocal transcriptional response.

Détails

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Etat: Serval
Version: de l'auteur
ID Serval
serval:BIB_8B036F457643
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
RNAseq analysis of heart tissue from mice treated with atenolol and isoproterenol reveals a reciprocal transcriptional response.
Périodique
BMC Genomics
Auteur(s)
Prunotto A., Stevenson B.J., Berthonneche C., Schüpfer F., Beckmann J.S., Maurer F., Bergmann S.
ISSN
1471-2164 (Electronic)
ISSN-L
1471-2164
Statut éditorial
Publié
Date de publication
2016
Peer-reviewed
Oui
Volume
17
Pages
717
Langue
anglais
Résumé
The transcriptional response to many widely used drugs and its modulation by genetic variability is poorly understood. Here we present an analysis of RNAseq profiles from heart tissue of 18 inbred mouse strains treated with the β-blocker atenolol (ATE) and the β-agonist isoproterenol (ISO).
Differential expression analyses revealed a large set of genes responding to ISO (n = 1770 at FDR = 0.0001) and a comparatively small one responding to ATE (n = 23 at FDR = 0.0001). At a less stringent definition of differential expression, the transcriptional responses to these two antagonistic drugs are reciprocal for many genes, with an overall anti-correlation of r = -0.3. This trend is also observed at the level of most individual strains even though the power to detect differential expression is significantly reduced. The inversely expressed gene sets are enriched with genes annotated for heart-related functions. Modular analysis revealed gene sets that exhibit coherent transcription profiles across some strains and/or treatments. Correlations between these modules and a broad spectrum of cardiovascular traits are stronger than expected by chance. This provides evidence for the overall importance of transcriptional regulation for these organismal responses and explicits links between co-expressed genes and the traits they are associated with. Gene set enrichment analysis of differentially expressed groups of genes pointed to pathways related to heart development and functionality.
Our study provides new insights into the transcriptional response of the heart to perturbations of the β-adrenergic system, implicating several new genes that had not been associated to this system previously.

Mots-clé
Mouse heart, beta-adrenergic system, Cardiac hypertrophy, RNAseq, Atenolol, Isoproterenol
Pubmed
Web of science
Open Access
Oui
Création de la notice
23/09/2016 20:13
Dernière modification de la notice
08/05/2019 21:41
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