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

103 Scopus citations

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

ASJC Scopus subject areas

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

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    Albinsson, S., Skoura, A., Yu, J., DiLorenzo, A., Fernández-Hernando, C., Offermanns, S., Miano, J. M., & 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