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01.12.2014 | Research article | Ausgabe 1/2014 Open Access

BMC Cardiovascular Disorders 1/2014

BRG1 overexpression in smooth muscle cells promotes the development of thoracic aortic dissection

Zeitschrift:
BMC Cardiovascular Disorders > Ausgabe 1/2014
Autoren:
Yang Yuan, Chong Wang, Jibin Xu, Jin Tao, Zhiyun Xu, Shengdong Huang
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1471-2261-14-144) contains supplementary material, which is available to authorized users.
Yang Yuan, Chong Wang, Jibin Xu contributed equally to this work.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

SDH and ZYX designed research and analyzed data. YY, CW, JBX and JT carried out molecular biology studies. YY, CW and JBX wrote the paper. All authors read and approved the final manuscript.

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.
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