The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Silencing MR-1 attenuates atherosclerosis in ApoE-/- mice induced by angiotensin II through FAK-Akt -mTOR-NF-kappaB signaling pathway

  • Chen, Yixi (Hunan Environment-Biological Polytechnic College) ;
  • Cao, Jianping (Hunan Environment-Biological Polytechnic College) ;
  • Zhao, Qihui (Hunan Environment-Biological Polytechnic College) ;
  • Luo, Haiyong (Hunan Environment-Biological Polytechnic College) ;
  • Wang, Yiguang (Key Lab of Antibiotic Biotechnology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences) ;
  • Dai, Wenjian (Hunan Environment-Biological Polytechnic College)
  • Received : 2017.05.18
  • Accepted : 2017.06.24
  • Published : 2018.03.01
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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 ($NF-{\kappa}B$) 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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References

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