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MicroRNAs are necessary for vascular smooth muscle growth, differentiation, and function

Albinsson, Sebastian LU ; Suarez, Yajaira; Skoura, Athanasia; Offermanns, Stefan; Miano, Joseph M and Sessa, William C (2010) In Arteriosclerosis, Thrombosis and Vascular Biology 30(6). p.26-1118
Abstract

OBJECTIVE: Regulation of vascular smooth muscle (VSM) proliferation and contractile differentiation is an important factor in vascular development and subsequent cardiovascular diseases. Recently, microRNAs (miRNAs) have been shown to regulate fundamental cellular processes in a number of cell types, but the integrated role of miRNAs in VSM in blood vessels is unknown. Here, we investigated the role of miRNAs in VSM by deleting the rate-limiting enzyme in miRNA synthesis, Dicer.

METHODS AND RESULTS: Deletion of Dicer in VSM results in late embryonic lethality at embryonic day 16 to 17, associated with extensive internal hemorrhage. The loss of VSM Dicer results in dilated, thin-walled blood vessels caused by a reduction in... (More)

OBJECTIVE: Regulation of vascular smooth muscle (VSM) proliferation and contractile differentiation is an important factor in vascular development and subsequent cardiovascular diseases. Recently, microRNAs (miRNAs) have been shown to regulate fundamental cellular processes in a number of cell types, but the integrated role of miRNAs in VSM in blood vessels is unknown. Here, we investigated the role of miRNAs in VSM by deleting the rate-limiting enzyme in miRNA synthesis, Dicer.

METHODS AND RESULTS: Deletion of Dicer in VSM results in late embryonic lethality at embryonic day 16 to 17, associated with extensive internal hemorrhage. The loss of VSM Dicer results in dilated, thin-walled blood vessels caused by a reduction in cellular proliferation. In addition, blood vessels from VSM-deleted Dicer mice exhibited impaired contractility because of a loss of contractile protein markers. We found this effect to be associated with a loss of actin stress fibers and partly rescued by overexpression of microRNA (miR)-145 or myocardin.

CONCLUSIONS: Dicer-dependent miRNAs are important for VSM development and function by regulating proliferation and contractile differentiation.

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author
publishing date
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Contribution to journal
publication status
published
keywords
Actins, Animals, Aorta, Cell Differentiation, Cell Proliferation, Cells, Cultured, DEAD-box RNA Helicases, Embryo Loss, Endoribonucleases, Gene Expression Regulation, Developmental, Genotype, Gestational Age, Hemorrhage, Integrases, Liver Diseases, Male, Mice, Mice, Knockout, MicroRNAs, Microfilament Proteins, Muscle Development, Muscle Proteins, Muscle, Smooth, Vascular, Nuclear Proteins, Phenotype, Ribonuclease III, Stress Fibers, Trans-Activators, Transcriptional Activation, Transfection, Umbilical Arteries, Vasoconstriction, Vasodilation
in
Arteriosclerosis, Thrombosis and Vascular Biology
volume
30
issue
6
pages
9 pages
publisher
American Heart Association
external identifiers
  • Scopus:77952885217
ISSN
1524-4636
DOI
10.1161/ATVBAHA.109.200873
language
English
LU publication?
no
id
41af3c2e-f268-401a-9b8c-f21ba5e44143
date added to LUP
2016-04-19 09:54:50
date last changed
2016-11-20 04:32:40
@misc{41af3c2e-f268-401a-9b8c-f21ba5e44143,
  abstract     = {<p>OBJECTIVE: Regulation of vascular smooth muscle (VSM) proliferation and contractile differentiation is an important factor in vascular development and subsequent cardiovascular diseases. Recently, microRNAs (miRNAs) have been shown to regulate fundamental cellular processes in a number of cell types, but the integrated role of miRNAs in VSM in blood vessels is unknown. Here, we investigated the role of miRNAs in VSM by deleting the rate-limiting enzyme in miRNA synthesis, Dicer.</p><p>METHODS AND RESULTS: Deletion of Dicer in VSM results in late embryonic lethality at embryonic day 16 to 17, associated with extensive internal hemorrhage. The loss of VSM Dicer results in dilated, thin-walled blood vessels caused by a reduction in cellular proliferation. In addition, blood vessels from VSM-deleted Dicer mice exhibited impaired contractility because of a loss of contractile protein markers. We found this effect to be associated with a loss of actin stress fibers and partly rescued by overexpression of microRNA (miR)-145 or myocardin.</p><p>CONCLUSIONS: Dicer-dependent miRNAs are important for VSM development and function by regulating proliferation and contractile differentiation.</p>},
  author       = {Albinsson, Sebastian and Suarez, Yajaira and Skoura, Athanasia and Offermanns, Stefan and Miano, Joseph M and Sessa, William C},
  issn         = {1524-4636},
  keyword      = {Actins,Animals,Aorta,Cell Differentiation,Cell Proliferation,Cells, Cultured,DEAD-box RNA Helicases,Embryo Loss,Endoribonucleases,Gene Expression Regulation, Developmental,Genotype,Gestational Age,Hemorrhage,Integrases,Liver Diseases,Male,Mice,Mice, Knockout,MicroRNAs,Microfilament Proteins,Muscle Development,Muscle Proteins,Muscle, Smooth, Vascular,Nuclear Proteins,Phenotype,Ribonuclease III,Stress Fibers,Trans-Activators,Transcriptional Activation,Transfection,Umbilical Arteries,Vasoconstriction,Vasodilation},
  language     = {eng},
  number       = {6},
  pages        = {26--1118},
  publisher    = {ARRAY(0xb010ce0)},
  series       = {Arteriosclerosis, Thrombosis and Vascular Biology},
  title        = {MicroRNAs are necessary for vascular smooth muscle growth, differentiation, and function},
  url          = {http://dx.doi.org/10.1161/ATVBAHA.109.200873},
  volume       = {30},
  year         = {2010},
}