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

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Serval ID
serval:BIB_8B036F457643
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
RNAseq analysis of heart tissue from mice treated with atenolol and isoproterenol reveals a reciprocal transcriptional response.
Journal
BMC Genomics
Author(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
Publication state
Published
Issued date
2016
Peer-reviewed
Oui
Volume
17
Pages
717
Language
english
Abstract
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.

Keywords
Mouse heart, beta-adrenergic system, Cardiac hypertrophy, RNAseq, Atenolol, Isoproterenol
Pubmed
Web of science
Open Access
Yes
Create date
23/09/2016 19:13
Last modification date
20/08/2019 14:49
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