Smooth muscle miRNAs are critical for post-natal regulation of blood pressure and vascular function.

Phenotypic modulation of smooth muscle cells (SMCs) plays a key role in vascular disease, including atherosclerosis. Several transcription factors have been suggested to regulate phenotypic modulation of SMCs but the decisive mechanisms remain unknown. Recent reports suggest that specific microRNAs...

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Main Authors: Sebastian Albinsson, Athanasia Skoura, Jun Yu, Annarita DiLorenzo, Carlos Fernández-Hernando, Stefan Offermanns, Joseph M Miano, William C Sessa
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2011-04-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3081311?pdf=render
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author Sebastian Albinsson
Athanasia Skoura
Jun Yu
Annarita DiLorenzo
Carlos Fernández-Hernando
Stefan Offermanns
Joseph M Miano
William C Sessa
author_facet Sebastian Albinsson
Athanasia Skoura
Jun Yu
Annarita DiLorenzo
Carlos Fernández-Hernando
Stefan Offermanns
Joseph M Miano
William C Sessa
author_sort Sebastian Albinsson
collection DOAJ
description Phenotypic modulation of smooth muscle cells (SMCs) plays a key role in vascular disease, including atherosclerosis. Several transcription factors have been suggested to regulate phenotypic modulation of SMCs but the decisive mechanisms remain unknown. Recent reports suggest that specific microRNAs (miRNAs) are involved in SMC differentiation and vascular disease but the global role of miRNAs in postnatal vascular SMC has not been elucidated. Thus, the objective of this study was to identify the role of Dicer-dependent miRNAs for blood pressure regulation and vascular SMC contractile function and differentiation in vivo. Tamoxifen-inducible and SMC specific deletion of Dicer was achieved by Cre-Lox recombination. Deletion of Dicer resulted in a global loss of miRNAs in aortic SMC. Furthermore, Dicer-deficient mice exhibited a dramatic reduction in blood pressure due to significant loss of vascular contractile function and SMC contractile differentiation as well as vascular remodeling. Several of these results are consistent with our previous observations in SM-Dicer deficient embryos. Therefore, miRNAs are essential for maintaining blood pressure and contractile function in resistance vessels. Although the phenotype of miR-143/145 deficient mice resembles the loss of Dicer, the phenotypes of SM-Dicer KO mice were far more severe suggesting that additional miRNAs are involved in maintaining postnatal SMC differentiation.
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spelling doaj.art-a7f8cc5ef7964823a03ac017e0158e832022-12-22T01:08:39ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-04-0164e1886910.1371/journal.pone.0018869Smooth muscle miRNAs are critical for post-natal regulation of blood pressure and vascular function.Sebastian AlbinssonAthanasia SkouraJun YuAnnarita DiLorenzoCarlos Fernández-HernandoStefan OffermannsJoseph M MianoWilliam C SessaPhenotypic modulation of smooth muscle cells (SMCs) plays a key role in vascular disease, including atherosclerosis. Several transcription factors have been suggested to regulate phenotypic modulation of SMCs but the decisive mechanisms remain unknown. Recent reports suggest that specific microRNAs (miRNAs) are involved in SMC differentiation and vascular disease but the global role of miRNAs in postnatal vascular SMC has not been elucidated. Thus, the objective of this study was to identify the role of Dicer-dependent miRNAs for blood pressure regulation and vascular SMC contractile function and differentiation in vivo. Tamoxifen-inducible and SMC specific deletion of Dicer was achieved by Cre-Lox recombination. Deletion of Dicer resulted in a global loss of miRNAs in aortic SMC. Furthermore, Dicer-deficient mice exhibited a dramatic reduction in blood pressure due to significant loss of vascular contractile function and SMC contractile differentiation as well as vascular remodeling. Several of these results are consistent with our previous observations in SM-Dicer deficient embryos. Therefore, miRNAs are essential for maintaining blood pressure and contractile function in resistance vessels. Although the phenotype of miR-143/145 deficient mice resembles the loss of Dicer, the phenotypes of SM-Dicer KO mice were far more severe suggesting that additional miRNAs are involved in maintaining postnatal SMC differentiation.http://europepmc.org/articles/PMC3081311?pdf=render
spellingShingle Sebastian Albinsson
Athanasia Skoura
Jun Yu
Annarita DiLorenzo
Carlos Fernández-Hernando
Stefan Offermanns
Joseph M Miano
William C Sessa
Smooth muscle miRNAs are critical for post-natal regulation of blood pressure and vascular function.
PLoS ONE
title Smooth muscle miRNAs are critical for post-natal regulation of blood pressure and vascular function.
title_full Smooth muscle miRNAs are critical for post-natal regulation of blood pressure and vascular function.
title_fullStr Smooth muscle miRNAs are critical for post-natal regulation of blood pressure and vascular function.
title_full_unstemmed Smooth muscle miRNAs are critical for post-natal regulation of blood pressure and vascular function.
title_short Smooth muscle miRNAs are critical for post-natal regulation of blood pressure and vascular function.
title_sort smooth muscle mirnas are critical for post natal regulation of blood pressure and vascular function
url http://europepmc.org/articles/PMC3081311?pdf=render
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