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

Sebastian Albinsson, Yajaira Suarez, Athanasia Skoura, Stefan Offermanns, Joseph M. Miano, William C. Sessa

Research output: Contribution to journalArticle

200 Scopus citations

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

Original languageEnglish (US)
Pages (from-to)1118-1126
Number of pages9
JournalArteriosclerosis, thrombosis, and vascular biology
Volume30
Issue number6
DOIs
StatePublished - Jun 2010

Keywords

  • Contractile proteins
  • Molecular biology
  • Vascular biology
  • Vascular muscle

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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