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

Albinsson, Sebastian LU ; Skoura, Athanasia; Yu, Jun; DiLorenzo, Annarita; Fernández-Hernando, Carlos; Offermanns, Stefan; Miano, Joseph M and Sessa, William C (2011) In PLoS One 6(4).
Abstract

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... (More)

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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Contribution to journal
publication status
published
keywords
Animals, Animals, Newborn, Aorta, Biomarkers, Blood Pressure, Cell Differentiation, Gene Deletion, Gene Expression Regulation, Heart Function Tests, Mice, Mice, Knockout, MicroRNAs, Muscle Contraction, Muscle, Smooth, Vascular, Myocardium, Myocytes, Smooth Muscle, Organ Specificity, Ribonuclease III, Weight Loss
in
PLoS One
volume
6
issue
4
publisher
Public Library of Science
external identifiers
  • Scopus:79955547741
ISSN
1932-6203
DOI
10.1371/journal.pone.0018869
language
English
LU publication?
no
id
a4510d19-d0e6-41f2-a0fe-198a0f618dcf
date added to LUP
2016-04-19 09:54:17
date last changed
2016-11-20 04:32:40
@misc{a4510d19-d0e6-41f2-a0fe-198a0f618dcf,
  abstract     = {<p>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.</p>},
  author       = {Albinsson, Sebastian and Skoura, Athanasia and Yu, Jun and DiLorenzo, Annarita and Fernández-Hernando, Carlos and Offermanns, Stefan and Miano, Joseph M and Sessa, William C},
  issn         = {1932-6203},
  keyword      = {Animals,Animals, Newborn,Aorta,Biomarkers,Blood Pressure,Cell Differentiation,Gene Deletion,Gene Expression Regulation,Heart Function Tests,Mice,Mice, Knockout,MicroRNAs,Muscle Contraction,Muscle, Smooth, Vascular,Myocardium,Myocytes, Smooth Muscle,Organ Specificity,Ribonuclease III,Weight Loss},
  language     = {eng},
  number       = {4},
  publisher    = {ARRAY(0x852c9f0)},
  series       = {PLoS One},
  title        = {Smooth muscle miRNAs are critical for post-natal regulation of blood pressure and vascular function},
  url          = {http://dx.doi.org/10.1371/journal.pone.0018869},
  volume       = {6},
  year         = {2011},
}