Heart Failure and MEF2 Transcriptome Dynamics in Response to β-Blockers

Abstract Myocyte Enhancer Factor 2 (MEF2) mediates cardiac remodelling in heart failure (HF) and is also a target of β-adrenergic signalling, a front-line treatment for HF. We identified global gene transcription networks involved in HF with and without β-blocker treatment. Experimental HF by transv...

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Autores principales:	S. W. Tobin, S. Hashemi, K. Dadson, S. Turdi, K. Ebrahimian, J. Zhao, G. Sweeney, J. Grigull, J. C. McDermott
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d8d5bdb28cbb420387d3534659928246
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spelling	oai:doaj.org-article:d8d5bdb28cbb420387d35346599282462021-12-02T16:06:32ZHeart Failure and MEF2 Transcriptome Dynamics in Response to β-Blockers10.1038/s41598-017-04762-x2045-2322https://doaj.org/article/d8d5bdb28cbb420387d35346599282462017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-04762-xhttps://doaj.org/toc/2045-2322Abstract Myocyte Enhancer Factor 2 (MEF2) mediates cardiac remodelling in heart failure (HF) and is also a target of β-adrenergic signalling, a front-line treatment for HF. We identified global gene transcription networks involved in HF with and without β-blocker treatment. Experimental HF by transverse aortic constriction (TAC) in a MEF2 “sensor” mouse model (6 weeks) was followed by four weeks of β-blockade with Atenolol (AT) or Solvent (Sol) treatment. Transcriptome analysis (RNA-seq) from left ventricular RNA samples and MEF2A depleted cardiomyocytes was performed. AT treatment resulted in an overall improvement in cardiac function of TAC mice and repression of MEF2 activity. RNA-seq identified 65 differentially expressed genes (DEGs) due to TAC treatment with enriched GO clusters including the inflammatory system, cell migration and apoptosis. These genes were mapped against DEGs in cardiomyocytes in which MEF2A expression was suppressed. Of the 65 TAC mediated DEGs, AT reversed the expression of 28 mRNAs. Rarres2 was identified as a novel MEF2 target gene that is upregulated with TAC in vivo and isoproterenol treatment in vitro which may have implications in cardiomyocyte apoptosis and hypertrophy. These studies identify a cohort of genes with vast potential for disease diagnosis and therapeutic intervention in heart failure.S. W. TobinS. HashemiK. DadsonS. TurdiK. EbrahimianJ. ZhaoG. SweeneyJ. GrigullJ. C. McDermottNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-14 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q S. W. Tobin S. Hashemi K. Dadson S. Turdi K. Ebrahimian J. Zhao G. Sweeney J. Grigull J. C. McDermott Heart Failure and MEF2 Transcriptome Dynamics in Response to β-Blockers
description	Abstract Myocyte Enhancer Factor 2 (MEF2) mediates cardiac remodelling in heart failure (HF) and is also a target of β-adrenergic signalling, a front-line treatment for HF. We identified global gene transcription networks involved in HF with and without β-blocker treatment. Experimental HF by transverse aortic constriction (TAC) in a MEF2 “sensor” mouse model (6 weeks) was followed by four weeks of β-blockade with Atenolol (AT) or Solvent (Sol) treatment. Transcriptome analysis (RNA-seq) from left ventricular RNA samples and MEF2A depleted cardiomyocytes was performed. AT treatment resulted in an overall improvement in cardiac function of TAC mice and repression of MEF2 activity. RNA-seq identified 65 differentially expressed genes (DEGs) due to TAC treatment with enriched GO clusters including the inflammatory system, cell migration and apoptosis. These genes were mapped against DEGs in cardiomyocytes in which MEF2A expression was suppressed. Of the 65 TAC mediated DEGs, AT reversed the expression of 28 mRNAs. Rarres2 was identified as a novel MEF2 target gene that is upregulated with TAC in vivo and isoproterenol treatment in vitro which may have implications in cardiomyocyte apoptosis and hypertrophy. These studies identify a cohort of genes with vast potential for disease diagnosis and therapeutic intervention in heart failure.
format	article
author	S. W. Tobin S. Hashemi K. Dadson S. Turdi K. Ebrahimian J. Zhao G. Sweeney J. Grigull J. C. McDermott
author_facet	S. W. Tobin S. Hashemi K. Dadson S. Turdi K. Ebrahimian J. Zhao G. Sweeney J. Grigull J. C. McDermott
author_sort	S. W. Tobin
title	Heart Failure and MEF2 Transcriptome Dynamics in Response to β-Blockers
title_short	Heart Failure and MEF2 Transcriptome Dynamics in Response to β-Blockers
title_full	Heart Failure and MEF2 Transcriptome Dynamics in Response to β-Blockers
title_fullStr	Heart Failure and MEF2 Transcriptome Dynamics in Response to β-Blockers
title_full_unstemmed	Heart Failure and MEF2 Transcriptome Dynamics in Response to β-Blockers
title_sort	heart failure and mef2 transcriptome dynamics in response to β-blockers
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/d8d5bdb28cbb420387d3534659928246
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Heart Failure and MEF2 Transcriptome Dynamics in Response to β-Blockers

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