Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3081311/ https://www.ncbi.nlm.nih.gov/pubmed/21526127 http://dx.doi.org/10.1371/journal.pone.0018869 |
_version_ | 1782202198167388160 |
---|---|
author | Albinsson, Sebastian Skoura, Athanasia Yu, Jun DiLorenzo, Annarita Fernández-Hernando, Carlos Offermanns, Stefan Miano, Joseph M. Sessa, William C. |
author_facet | Albinsson, Sebastian Skoura, Athanasia Yu, Jun DiLorenzo, Annarita Fernández-Hernando, Carlos Offermanns, Stefan Miano, Joseph M. Sessa, William C. |
author_sort | Albinsson, Sebastian |
collection | PubMed |
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. |
format | Text |
id | pubmed-3081311 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-30813112011-04-27 Smooth Muscle miRNAs Are Critical for Post-Natal Regulation of Blood Pressure and Vascular Function Albinsson, Sebastian Skoura, Athanasia Yu, Jun DiLorenzo, Annarita Fernández-Hernando, Carlos Offermanns, Stefan Miano, Joseph M. Sessa, William C. PLoS One Research Article 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. Public Library of Science 2011-04-22 /pmc/articles/PMC3081311/ /pubmed/21526127 http://dx.doi.org/10.1371/journal.pone.0018869 Text en Albinsson et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Albinsson, Sebastian Skoura, Athanasia Yu, Jun DiLorenzo, Annarita Fernández-Hernando, Carlos Offermanns, Stefan Miano, Joseph M. Sessa, William C. Smooth Muscle miRNAs Are Critical for Post-Natal Regulation of Blood Pressure and Vascular Function |
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 |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3081311/ https://www.ncbi.nlm.nih.gov/pubmed/21526127 http://dx.doi.org/10.1371/journal.pone.0018869 |
work_keys_str_mv | AT albinssonsebastian smoothmusclemirnasarecriticalforpostnatalregulationofbloodpressureandvascularfunction AT skouraathanasia smoothmusclemirnasarecriticalforpostnatalregulationofbloodpressureandvascularfunction AT yujun smoothmusclemirnasarecriticalforpostnatalregulationofbloodpressureandvascularfunction AT dilorenzoannarita smoothmusclemirnasarecriticalforpostnatalregulationofbloodpressureandvascularfunction AT fernandezhernandocarlos smoothmusclemirnasarecriticalforpostnatalregulationofbloodpressureandvascularfunction AT offermannsstefan smoothmusclemirnasarecriticalforpostnatalregulationofbloodpressureandvascularfunction AT mianojosephm smoothmusclemirnasarecriticalforpostnatalregulationofbloodpressureandvascularfunction AT sessawilliamc smoothmusclemirnasarecriticalforpostnatalregulationofbloodpressureandvascularfunction |