title: BRG1 overexpression in smooth muscle cells promotes the development of thoracic aortic dissection.
abstract: BACKGROUND
  Here we investigated Brahma-related gene 1 (BRG1) expression in aortic smooth muscle cells (SMCs) and its role in the regulation of the pathological changes in aortic SMCs of thoracic arotic dissection (TAD).
  
  
  METHODS
  BRG1, matrix metalloproteinase 2 (MMP2), and MMP9 mRNA and protein expression in human aortic specimens were examined by qPCR and western blot, respectively. The percentage of apoptotic and contractile SMCs in aortic specimens were determined by TUNEL assay and α-SMA immunohistochemical staining, respectively. The role of BRG1 in MMP2 and MMP9 expression, cell apoptosis, and phenotype transition in aortic SMCs were investigated using a human aortic SMC line via adenovirus mediated gene transfer. MMPs mRNA and protein levels were analyzed by qPCR and western blot, respectively. The percentage of apoptotic and contractile cells were determined through flow cytometry analysis.
  
  
  RESULTS
  The expression level of BRG1 in the aortic walls (adventitia-removed) was significantly higher in the TAD than the normal group. BRG1 expression was positively correlated to expression of MMP2 and MMP9 and SMC apoptosis, but was negatively correlated to the percentage of contractile aortic SMCs in TAD specimens. In human aortic SMC line, BRG1 transfection led to significant upregulation of MMP2 and MMP9 expression and a concomitant increase in SMC apoptosis as well as a decrease in the percentage of contractile phenotype of cells.
  
  
  CONCLUSIONS
  BRG1 is significantly upregulated in the aortic SMCs of TAD, and its overexpression might promote the development of TAD by increasing MMP2 and MMP9 expression, inducing SMC apoptosis and the transition from contractile to synthetic phenotype.
authors.affiliation: Institute of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, 168, Changhai Rd, Shanghai, P. R. China. iamyuanyang@gmail.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, 168, Changhai Rd., Shanghai, P. R. China. drwangchong@hotmail.com.
authors.forename: Chong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, 168, Changhai Rd., Shanghai, P. R. China. xujibin@163.com.
authors.forename: Jibin
authors.initials: J
authors.lastname: Xu
authors.affiliation: Institute of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, 168, Changhai Rd, Shanghai, P. R. China. taojing1997@163.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Tao
authors.affiliation: Department of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, 168, Changhai Rd., Shanghai, P. R. China. zhiyunxu@gmail.com.
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Institute of Cardiothoracic Surgery, Changhai Hospital, Second Military Medical University, 168, Changhai Rd, Shanghai, P. R. China. huangsd@smmu.edu.cn.
authors.forename: Shengdong
authors.initials: S
authors.lastname: Huang
mesh_terms: D000199:Actins / Q000378:metabolism; D000784:Aortic Dissection / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D001013:Aorta, Thoracic / Q000378:metabolism / Q000473:pathology; D017545:Aortic Aneurysm, Thoracic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D017209:Apoptosis; D016022:Case-Control Studies; D002478:Cells, Cultured; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D004108:Dilatation, Pathologic; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D015854:Up-Regulation; D014661:Vasoconstriction
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C084108:SMARCA4 protein, human; D004265:DNA Helicases