Elevated miR-499 levels blunt the cardiac stress response.

<h4>Background</h4>The heart responds to myriad stresses by well-described transcriptional responses that involve long-term changes in gene expression as well as more immediate, transient adaptations. MicroRNAs quantitatively regulate mRNAs and thus may affect the cardiac transcriptional...

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Autores principales:	Joseph T C Shieh, Yu Huang, Jacqueline Gilmore, Deepak Srivastava
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b6d57590a7e3409bbc63256915d053b6
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id	oai:doaj.org-article:b6d57590a7e3409bbc63256915d053b6
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spelling	oai:doaj.org-article:b6d57590a7e3409bbc63256915d053b62021-11-18T06:54:14ZElevated miR-499 levels blunt the cardiac stress response.1932-620310.1371/journal.pone.0019481https://doaj.org/article/b6d57590a7e3409bbc63256915d053b62011-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21573063/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The heart responds to myriad stresses by well-described transcriptional responses that involve long-term changes in gene expression as well as more immediate, transient adaptations. MicroRNAs quantitatively regulate mRNAs and thus may affect the cardiac transcriptional output and cardiac function. Here we investigate miR-499, a microRNA embedded within a ventricular-specific myosin heavy chain gene, which is expressed in heart and skeletal muscle.<h4>Methodology/principal findings</h4>We assessed miR-499 expression in human tissue to confirm its potential relevance to human cardiac gene regulation. Using a transgenic mouse model, we found that elevated miR-499 levels caused cellular hypertrophy and cardiac dysfunction in a dose-dependent manner. Global gene expression profiling revealed altered levels of the immediate early stress response genes (Egr1, Egr2 and Fos), ß-myosin heavy chain (Myh7), and skeletal muscle actin (Acta1). We verified the effect of miR-499 on the immediate early response genes by miR-499 gain- and loss-of-function in vitro. Consistent with a role for miR-499 in blunting the response to cardiac stress, asymptomatic miR-499-expressing mice had an impaired response to pressure overload and accentuated cardiac dysfunction.<h4>Conclusions</h4>Elevated miR-499 levels affect cardiac gene expression and predispose to cardiac stress-induced dysfunction. miR-499 may titrate the cardiac response to stress in part by regulating the immediate early gene response.Joseph T C ShiehYu HuangJacqueline GilmoreDeepak SrivastavaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 5, p e19481 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Joseph T C Shieh Yu Huang Jacqueline Gilmore Deepak Srivastava Elevated miR-499 levels blunt the cardiac stress response.
description	<h4>Background</h4>The heart responds to myriad stresses by well-described transcriptional responses that involve long-term changes in gene expression as well as more immediate, transient adaptations. MicroRNAs quantitatively regulate mRNAs and thus may affect the cardiac transcriptional output and cardiac function. Here we investigate miR-499, a microRNA embedded within a ventricular-specific myosin heavy chain gene, which is expressed in heart and skeletal muscle.<h4>Methodology/principal findings</h4>We assessed miR-499 expression in human tissue to confirm its potential relevance to human cardiac gene regulation. Using a transgenic mouse model, we found that elevated miR-499 levels caused cellular hypertrophy and cardiac dysfunction in a dose-dependent manner. Global gene expression profiling revealed altered levels of the immediate early stress response genes (Egr1, Egr2 and Fos), ß-myosin heavy chain (Myh7), and skeletal muscle actin (Acta1). We verified the effect of miR-499 on the immediate early response genes by miR-499 gain- and loss-of-function in vitro. Consistent with a role for miR-499 in blunting the response to cardiac stress, asymptomatic miR-499-expressing mice had an impaired response to pressure overload and accentuated cardiac dysfunction.<h4>Conclusions</h4>Elevated miR-499 levels affect cardiac gene expression and predispose to cardiac stress-induced dysfunction. miR-499 may titrate the cardiac response to stress in part by regulating the immediate early gene response.
format	article
author	Joseph T C Shieh Yu Huang Jacqueline Gilmore Deepak Srivastava
author_facet	Joseph T C Shieh Yu Huang Jacqueline Gilmore Deepak Srivastava
author_sort	Joseph T C Shieh
title	Elevated miR-499 levels blunt the cardiac stress response.
title_short	Elevated miR-499 levels blunt the cardiac stress response.
title_full	Elevated miR-499 levels blunt the cardiac stress response.
title_fullStr	Elevated miR-499 levels blunt the cardiac stress response.
title_full_unstemmed	Elevated miR-499 levels blunt the cardiac stress response.
title_sort	elevated mir-499 levels blunt the cardiac stress response.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/b6d57590a7e3409bbc63256915d053b6
work_keys_str_mv	AT josephtcshieh elevatedmir499levelsbluntthecardiacstressresponse AT yuhuang elevatedmir499levelsbluntthecardiacstressresponse AT jacquelinegilmore elevatedmir499levelsbluntthecardiacstressresponse AT deepaksrivastava elevatedmir499levelsbluntthecardiacstressresponse
_version_	1718424251284848640

Elevated miR-499 levels blunt the cardiac stress response.

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