title: BRG1 expression is increased in thoracic aortic aneurysms and regulates proliferation and apoptosis of vascular smooth muscle cells through the long non-coding RNA HIF1A-AS1 in vitro.
abstract: OBJECTIVE
  Brahma-related gene 1 (BRG1) and long non-coding RNAs (lncRNAs) play important roles in cellular processes. However, little is known regarding their roles in thoracic aortic aneurysms. We investigated BRG1 expression in thoracic aortic aneurysms and the roles of BRG1 and the lncRNA HIF 1 alpha-antisense RNA 1 in regulating the proliferation and apoptosis of aortic smooth muscle cells in vitro.
  
  
  METHODS
  BRG1 mRNA and protein expression in human aortic media specimens were examined by quantitative real-time polymerase chain reaction, immunohistochemical staining and western blot. BRG1 expression was up-regulated by lentiviral vectors. Vascular smooth muscle cell proliferation and apoptosis were studied using Cell Counting Kit-8 and terminal deoxynucleotidyl transferase dUTP nick-end labelling assays. We performed western blots to detect Caspase3 and Bcl2 protein expression. LncRNAs regulated by BRG1 were identified through microarray in BRG1 gain- and loss-of-function vascular smooth muscle cells. Finally, the expression of HIF 1 alpha-antisense RNA 1 was reduced by siRNA and cell proliferation and apoptosis was studied using Cell Counting Kit-8 assays, caspase-3 activity assays and western blot.
  
  
  RESULTS
  BRG1 expression in the aortic media was significantly higher in thoracic aortic aneurysms than in normal controls. Overexpression of BRG1 in human aortic smooth muscle cells promoted apoptosis and reduced proliferation. The expression of HIF 1 alpha-antisense RNA 1 was significantly down- and up-regulated in BRG1 knock-down and overexpressing vascular smooth muscle cells, respectively. We further demonstrated that suppression of HIF 1 alpha-antisense RNA 1 by siRNA in vascular smooth muscle cells reduced apoptosis and promoted proliferation.
  
  
  CONCLUSIONS
  BRG1 is overexpressed in the aortic media of thoracic aortic aneurysms and the interaction between BRG1 and HIF 1 alpha-antisense RNA 1 plays a key role in the proliferation and apoptosis of vascular smooth muscle cells in vitro, which may contribute to the pathogenesis of thoracic aortic aneurysms.
authors.affiliation: Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China Department of Cardiothoracic Surgery, No. 153 Hospital of Liberation Army, Zhengzhou, Henan Province, China.
authors.forename: Shuwei
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Xiwu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Mengwei
authors.initials: M
authors.lastname: Tan
authors.affiliation: Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Le
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Xue
authors.affiliation: Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Han
authors.affiliation: Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China zhiyunx@hotmail.com.
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Xu
mesh_terms: D001013:Aorta, Thoracic / Q000737:chemistry / Q000378:metabolism; D017545:Aortic Aneurysm, Thoracic / Q000378:metabolism*; D017209:Apoptosis / Q000235:genetics*; D002460:Cell Line; D049109:Cell Proliferation / Q000235:genetics*; D004265:DNA Helicases / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D020868:Gene Silencing; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000378:metabolism*; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics / Q000378:metabolism*
chemical_list: C497442:HIF1A protein, human; C000608170:HIF1A-AS1 long non-coding RNA, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D062085:RNA, Long Noncoding; D014157:Transcription Factors; C084108:SMARCA4 protein, human; D004265:DNA Helicases
keywords: Apoptosis; Brahma-related gene 1; Long non-coding RNA; Proliferation; Thoracic aortic aneurysm; Vascular smooth muscle cells