title: MicroRNA-21 regulates vascular smooth muscle cell function via targeting tropomyosin 1 in arteriosclerosis obliterans of lower extremities.
abstract: OBJECTIVE
  The goal of this study was to determine the expression signature and the potential role of microRNAs in human arteries with arteriosclerosis obliterans (ASO).
  
  
  RESULTS
  The expression profiles of microRNAs in human arteries with ASO and in normal control arteries were determined by quantitative reverse transcription-polymerase chain reaction array. Among the 617 detected microRNAs, multiple microRNAs were aberrantly expressed in arteries with ASO. Some of these dysregulated microRNAs were further verified by quantitative reverse transcription-polymerase chain reaction. Among them, microRNA-21 (miR-21) was mainly located in arterial smooth muscle cells (ASMCs) and was increased by more than 7-fold in ASO that was related to hypoxia inducible factor 1-α. In cultured human ASMCs, cell proliferation and migration were significantly decreased by inhibition of miR-21. 3'-Untranslated region luciferase assay confirmed that tropomyosin 1 was a target of miR-21 that was involved in miR-21-mediated cellular effects, such as cell shape modulation.
  
  
  CONCLUSIONS
  The results suggest that miR-21 is able to regulate ASMC function by targeting tropomyosin 1. The hypoxia inducible factor-1 α/miR-21/tropomyosin 1 pathway may play a critical role in the pathogenesis of ASO. These findings might provide a new therapeutic target for human ASO.
authors.affiliation: Division of Vascular Surgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
authors.forename: Mian
authors.initials: M
authors.lastname: Wang
authors.forename: Wen
authors.initials: W
authors.lastname: Li
authors.forename: Guang-Qi
authors.initials: GQ
authors.lastname: Chang
authors.forename: Cai-Sheng
authors.initials: CS
authors.lastname: Ye
authors.forename: Jing-Song
authors.initials: JS
authors.lastname: Ou
authors.forename: Xiao-Xi
authors.initials: XX
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
authors.forename: Tuck-Yun
authors.initials: TY
authors.lastname: Cheang
authors.forename: Xue-Ling
authors.initials: XL
authors.lastname: Huang
authors.forename: Shen-Ming
authors.initials: SM
authors.lastname: Wang
mesh_terms: D000199:Actins / Q000737:chemistry; D001162:Arteriosclerosis Obliterans / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology; D035002:Lower Extremity / Q000503:physiopathology*; D035683:MicroRNAs / Q000032:analysis / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D014335:Tropomyosin / Q000737:chemistry / Q000502:physiology*
chemical_list: D000199:Actins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; C490775:TPM1 protein, human; D014335:Tropomyosin