Silencing MR-1 attenuates atherosclerosis in ApoE(−/−) mice induced by angiotensin II through FAK-Akt–mTOR-NF-kappaB signaling pathway
The Korean Journal of Physiology and Pharmacology
;
: 127-134, 2018.
Artigo
em Inglês
| WPRIM
| ID: wpr-728629
ABSTRACT
Myofibrillogenesis regulator-1 (MR-1) is a novel protein involved in cellular proliferation, migration, inflammatory reaction and signal transduction. However, little information is available on the relationship between MR-1 expression and the progression of atherosclerosis. Here we report atheroprotective effects of silencing MR-1 in a model of Ang II-accelerated atherosclerosis, characterized by suppression focal adhesion kinase (FAK) and nuclear factor kappaB (NF-κB) signaling pathway, and atherosclerotic lesion macrophage content. In this model, administration of the siRNA-MR-1 substantially attenuated Ang II-accelerated atherosclerosis with stabilization of atherosclerotic plaques and inhibited FAK, Akt, mammalian target of rapamycin (mTOR) and NF-kB activation, which was associated with suppression of inflammatory factor and atherogenic gene expression in the artery. In vitro studies demonstrated similar changes in Ang II-treated vascular smooth muscle cells (VSMCs) and macrophages siRNA-MR-1 inhibited the expression levels of proinflammatory factor. These studies uncover crucial proinflammatory mechanisms of Ang II and highlight actions of silencing MR-1 to inhibit Ang II signaling, which is atheroprotective.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Artérias
/
Técnicas In Vitro
/
Angiotensina II
/
Angiotensinas
/
Transdução de Sinais
/
Expressão Gênica
/
NF-kappa B
/
Sirolimo
/
Desenvolvimento Muscular
/
RNA Interferente Pequeno
Tipo de estudo:
Estudo prognóstico
Limite:
Animais
Idioma:
Inglês
Revista:
The Korean Journal of Physiology and Pharmacology
Ano de publicação:
2018
Tipo de documento:
Artigo
Similares
MEDLINE
...
LILACS
LIS