Silencing MR-1 attenuates atherosclerosis in ApoE(−/−) mice induced by angiotensin II through FAK-Akt–mTOR-NF-kappaB signaling pathway.
10.4196/kjpp.2018.22.2.127
- Author:
Yixi CHEN
1
;
Jianping CAO
;
Qihui ZHAO
;
Haiyong LUO
;
Yiguang WANG
;
Wenjian DAI
Author Information
1. Hunan Environment-Biological Polytechnic College, Hengyang Hunan 421005, China. wjdai@126.com
- Publication Type:Original Article
- Keywords:
Angiotensin II;
Apolipoprotein E;
Atherosclerosis;
Myofibrillogenesis regulator-1;
NF-κB;
siRNA
- MeSH:
Angiotensin II*;
Angiotensins*;
Animals;
Arteries;
Atherosclerosis*;
Cell Proliferation;
Focal Adhesion Protein-Tyrosine Kinases;
Gene Expression;
In Vitro Techniques;
Macrophages;
Mice*;
Muscle Development;
Muscle, Smooth, Vascular;
NF-kappa B;
Plaque, Atherosclerotic;
RNA, Small Interfering;
Signal Transduction;
Sirolimus
- From:The Korean Journal of Physiology and Pharmacology
2018;22(2):127-134
- CountryRepublic of Korea
- Language:English
-
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.
