title: MicroRNAs are necessary for vascular smooth muscle growth, differentiation, and function.
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.
  
  
  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.
authors.affiliation: Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Albinsson
authors.forename: Yajaira
authors.initials: Y
authors.lastname: Suarez
authors.forename: Athanasia
authors.initials: A
authors.lastname: Skoura
authors.forename: Stefan
authors.initials: S
authors.lastname: Offermanns
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Miano
authors.forename: William C
authors.initials: WC
authors.lastname: Sessa
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D002478:Cells, Cultured; D053487:DEAD-box RNA Helicases / Q000172:deficiency / Q000235:genetics; D020964:Embryo Loss; D004722:Endoribonucleases / Q000172:deficiency / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D005865:Gestational Age; D006470:Hemorrhage / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D019426:Integrases / Q000235:genetics; D008107:Liver Diseases / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000378:metabolism*; D008840:Microfilament Proteins / Q000235:genetics; D024510:Muscle Development / Q000235:genetics; D009124:Muscle Proteins / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000196:embryology / Q000378:metabolism* / Q000503:physiopathology / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D043244:Ribonuclease III; D022502:Stress Fibers / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection; D014469:Umbilical Arteries / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D014661:Vasoconstriction / Q000235:genetics; D014664:Vasodilation / Q000235:genetics; D000099251:Myocardin
chemical_list: D000199:Actins; D053487:DEAD-box RNA Helicases; D004722:Endoribonucleases; D019426:Integrases; D035683:MicroRNAs; D008840:Microfilament Proteins; D009124:Muscle Proteins; D009687:Nuclear Proteins; D043244:Ribonuclease III; D015534:Trans-Activators; D000099251:Myocardin; C543499:MIRN145a microRNA, mouse; C058992:Tagln protein, mouse; C045073:Cre recombinase; C509781:Dicer1 protein, mouse