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KMID : 0811720180220020127
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Korean Journal of Physiology & Pharmacology
2018 Volume.22 No. 2 p.127 ~ p.134
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Silencing MR-1 attenuates atherosclerosis in ApoE?/? mice induced by angiotensin II through FAK-Akt ?mTOR-NF-kappaB signaling pathway
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Chen Yixi
Cao Jianping
Zhao Qihui
Luo Haiyong
Wang Yiguang
Dai Wenjian
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Abstract
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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.
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KEYWORD
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Angiotensin II, Apolipoprotein E, Atherosclerosis, Myofibrillogenesis regulator-1, NF-κB, siRNA
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