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

Sebastian Albinsson, Athanasia Skoura, Jun Yu, Annarita DiLorenzo, Carlos Fernández-Hernando, Stefan Offermanns, Joseph M. Miano, William C. Sessa

Research output: Contribution to journalArticle

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 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.

Original languageEnglish (US)
Article numbere18869
JournalPloS one
Volume6
Issue number4
DOIs
StatePublished - May 4 2011
Externally publishedYes

Fingerprint

Blood pressure
MicroRNAs
microRNA
blood vessels
smooth muscle
myocytes
Smooth Muscle Myocytes
blood pressure
Smooth Muscle
Blood Vessels
Muscle
Blood Pressure
Cell Differentiation
vascular diseases
Vascular Diseases
Vascular Smooth Muscle
cell differentiation
mice
Pressure regulation
Modulation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Cite this

Albinsson, S., Skoura, A., Yu, J., DiLorenzo, A., Fernández-Hernando, C., Offermanns, S., ... Sessa, W. C. (2011). Smooth muscle miRNAs are critical for post-natal regulation of blood pressure and vascular function. PloS one, 6(4), [e18869]. https://doi.org/10.1371/journal.pone.0018869

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.

In: PloS one, Vol. 6, No. 4, e18869, 04.05.2011.

Research output: Contribution to journalArticle

Albinsson, S, Skoura, A, Yu, J, DiLorenzo, A, Fernández-Hernando, C, Offermanns, S, Miano, JM & Sessa, WC 2011, 'Smooth muscle miRNAs are critical for post-natal regulation of blood pressure and vascular function', PloS one, vol. 6, no. 4, e18869. https://doi.org/10.1371/journal.pone.0018869
Albinsson S, Skoura A, Yu J, DiLorenzo A, Fernández-Hernando C, Offermanns S et al. Smooth muscle miRNAs are critical for post-natal regulation of blood pressure and vascular function. PloS one. 2011 May 4;6(4). e18869. https://doi.org/10.1371/journal.pone.0018869
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. In: PloS one. 2011 ; Vol. 6, No. 4.
@article{1c9c868fe11749f290ff89acb79be23b,
title = "Smooth muscle miRNAs are critical for post-natal regulation of blood pressure and vascular function",
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 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.",
author = "Sebastian Albinsson and Athanasia Skoura and Jun Yu and Annarita DiLorenzo and Carlos Fern{\'a}ndez-Hernando and Stefan Offermanns and Miano, {Joseph M.} and Sessa, {William C.}",
year = "2011",
month = "5",
day = "4",
doi = "10.1371/journal.pone.0018869",
language = "English (US)",
volume = "6",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "4",

}

TY - JOUR

T1 - Smooth muscle miRNAs are critical for post-natal regulation of blood pressure and vascular function

AU - Albinsson, Sebastian

AU - Skoura, Athanasia

AU - Yu, Jun

AU - DiLorenzo, Annarita

AU - Fernández-Hernando, Carlos

AU - Offermanns, Stefan

AU - Miano, Joseph M.

AU - Sessa, William C.

PY - 2011/5/4

Y1 - 2011/5/4

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=79955547741&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79955547741&partnerID=8YFLogxK

U2 - 10.1371/journal.pone.0018869

DO - 10.1371/journal.pone.0018869

M3 - Article

C2 - 21526127

AN - SCOPUS:79955547741

VL - 6

JO - PLoS One

JF - PLoS One

SN - 1932-6203

IS - 4

M1 - e18869

ER -