Global microRNA profiling of the mouse ventricles during development of severe hypertrophic cardiomyopathy and heart failure.

MicroRNAs (miRNAs) regulate post-transcriptional gene expression during development and disease. We have determined the miRNA expression levels of early- and end-stage hypertrophic cardiomyopathy (HCM) in a severe, transgenic mouse model of the disease. Five miRNAs were differentially expressed at a...

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Autores principales:	Richard D Bagnall, Tatiana Tsoutsman, Rhian E Shephard, William Ritchie, Christopher Semsarian
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/54c9e277339248f1b3d06f906e6953ef
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spelling	oai:doaj.org-article:54c9e277339248f1b3d06f906e6953ef2021-11-18T07:05:32ZGlobal microRNA profiling of the mouse ventricles during development of severe hypertrophic cardiomyopathy and heart failure.1932-620310.1371/journal.pone.0044744https://doaj.org/article/54c9e277339248f1b3d06f906e6953ef2012-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0044744https://doaj.org/toc/1932-6203MicroRNAs (miRNAs) regulate post-transcriptional gene expression during development and disease. We have determined the miRNA expression levels of early- and end-stage hypertrophic cardiomyopathy (HCM) in a severe, transgenic mouse model of the disease. Five miRNAs were differentially expressed at an early stage of HCM development. Time-course analysis revealed that decreased expression of miR-1 and miR-133a commences at a pre-disease stage, and precedes upregulation of target genes causal of cardiac hypertrophy and extracellular matrix remodelling, suggesting a role for miR-1 and miR-133a in early disease development. At end-stage HCM, 16 miRNA are dysregulated to form an expression profile resembling that of other forms of cardiac hypertrophy, suggesting common responses. Analysis of the mRNA transcriptome revealed that miRNAs potentially target 15.7% upregulated and 4.8% downregulated mRNAs at end-stage HCM, and regulate mRNAs associated with cardiac hypertrophy and electrophysiology, calcium signalling, fibrosis, and the TGF-β signalling pathway. Collectively, these results define the miRNA expression signatures during development and progression of severe HCM and highlight critical miRNA regulated gene networks that are involved in disease pathogenesis.Richard D BagnallTatiana TsoutsmanRhian E ShephardWilliam RitchieChristopher SemsarianPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e44744 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Richard D Bagnall Tatiana Tsoutsman Rhian E Shephard William Ritchie Christopher Semsarian Global microRNA profiling of the mouse ventricles during development of severe hypertrophic cardiomyopathy and heart failure.
description	MicroRNAs (miRNAs) regulate post-transcriptional gene expression during development and disease. We have determined the miRNA expression levels of early- and end-stage hypertrophic cardiomyopathy (HCM) in a severe, transgenic mouse model of the disease. Five miRNAs were differentially expressed at an early stage of HCM development. Time-course analysis revealed that decreased expression of miR-1 and miR-133a commences at a pre-disease stage, and precedes upregulation of target genes causal of cardiac hypertrophy and extracellular matrix remodelling, suggesting a role for miR-1 and miR-133a in early disease development. At end-stage HCM, 16 miRNA are dysregulated to form an expression profile resembling that of other forms of cardiac hypertrophy, suggesting common responses. Analysis of the mRNA transcriptome revealed that miRNAs potentially target 15.7% upregulated and 4.8% downregulated mRNAs at end-stage HCM, and regulate mRNAs associated with cardiac hypertrophy and electrophysiology, calcium signalling, fibrosis, and the TGF-β signalling pathway. Collectively, these results define the miRNA expression signatures during development and progression of severe HCM and highlight critical miRNA regulated gene networks that are involved in disease pathogenesis.
format	article
author	Richard D Bagnall Tatiana Tsoutsman Rhian E Shephard William Ritchie Christopher Semsarian
author_facet	Richard D Bagnall Tatiana Tsoutsman Rhian E Shephard William Ritchie Christopher Semsarian
author_sort	Richard D Bagnall
title	Global microRNA profiling of the mouse ventricles during development of severe hypertrophic cardiomyopathy and heart failure.
title_short	Global microRNA profiling of the mouse ventricles during development of severe hypertrophic cardiomyopathy and heart failure.
title_full	Global microRNA profiling of the mouse ventricles during development of severe hypertrophic cardiomyopathy and heart failure.
title_fullStr	Global microRNA profiling of the mouse ventricles during development of severe hypertrophic cardiomyopathy and heart failure.
title_full_unstemmed	Global microRNA profiling of the mouse ventricles during development of severe hypertrophic cardiomyopathy and heart failure.
title_sort	global microrna profiling of the mouse ventricles during development of severe hypertrophic cardiomyopathy and heart failure.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/54c9e277339248f1b3d06f906e6953ef
work_keys_str_mv	AT richarddbagnall globalmicrornaprofilingofthemouseventriclesduringdevelopmentofseverehypertrophiccardiomyopathyandheartfailure AT tatianatsoutsman globalmicrornaprofilingofthemouseventriclesduringdevelopmentofseverehypertrophiccardiomyopathyandheartfailure AT rhianeshephard globalmicrornaprofilingofthemouseventriclesduringdevelopmentofseverehypertrophiccardiomyopathyandheartfailure AT williamritchie globalmicrornaprofilingofthemouseventriclesduringdevelopmentofseverehypertrophiccardiomyopathyandheartfailure AT christophersemsarian globalmicrornaprofilingofthemouseventriclesduringdevelopmentofseverehypertrophiccardiomyopathyandheartfailure
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Global microRNA profiling of the mouse ventricles during development of severe hypertrophic cardiomyopathy and heart failure.

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