BRG1 overexpression in smooth muscle cells promotes the development of thoracic aortic dissection.
BMC Cardiovasc Disord
; 14: 144, 2014 Oct 11.
Article
en En
| MEDLINE
| ID: mdl-25304030
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
6_cardiovascular_diseases
Asunto principal:
Factores de Transcripción
/
Proteínas Nucleares
/
Aneurisma de la Aorta Torácica
/
ADN Helicasas
/
Miocitos del Músculo Liso
/
Disección Aórtica
/
Músculo Liso Vascular
Tipo de estudio:
Observational_studies
Límite:
Humans
Idioma:
En
Revista:
BMC Cardiovasc Disord
Asunto de la revista:
ANGIOLOGIA
/
CARDIOLOGIA
Año:
2014
Tipo del documento:
Article