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

Research output: Contribution to journalArticle

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 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.

Details

Authors
  • Sebastian Albinsson
  • Yajaira Suarez
  • Athanasia Skoura
  • Stefan Offermanns
  • Joseph M Miano
  • William C Sessa
External organisations
  • Yale University
Research areas and keywords

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
Original languageEnglish
Pages (from-to)1118-26
Number of pages9
JournalArteriosclerosis, Thrombosis and Vascular Biology
Volume30
Issue number6
Publication statusPublished - 2010 Jun
Publication categoryResearch
Peer-reviewedYes
Externally publishedYes