Rapamycin attenuates a murine model of thoracic aortic aneurysm by downregulating the miR-126-3p mediated activation of MAPK/ERK signalling pathway.
Biochem Biophys Res Commun
; 512(3): 498-504, 2019 05 07.
Article
em En
| MEDLINE
| ID: mdl-30904162
ABSTRACT
Thoracic aortic aneurysm (TAA) is fatal diseases, which leads to aortic rupture and sudden death. Blood pressure-lowering drugs are ineffective for most of the patients. Our previous study demonstrated the inhibition of endothelial secreted miR-126-3p by rapamycin ameliorate the aneurysmal phenotype of smooth muscle cells (SMCs) in vitro. Hence, this study aimed to evaluate the modulation and mechanism of miR-126-3p in a murine model of TAA (Fbn1C1039G/+). Our results showed that noticeable disturbed flow (DF) was observed in the aorta of Fbn1C1039G/+ mice, and the expression of miR-126-3p was significantly increased under the DF in the cell chamber. This finding was also confirmed by tests in the corresponding DF area of the human aortic aneurysm tissue. Constant rapamycin administration significantly ameliorates the incidence and severity of Fbn1C1039G/+ mice characterized by decreased aortic media degradation, macrophage infiltration and MMP2/9 expression in the aortic wall. Mechanistic studies showed that rapamycin attenuates TAA progression by inhibiting miR-126-3p through ERK1/2 inactivation.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Aneurisma da Aorta Torácica
/
Sirolimo
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Sistema de Sinalização das MAP Quinases
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MicroRNAs
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Antibacterianos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Ano de publicação:
2019
Tipo de documento:
Article