Silencing MR-1 attenuates atherosclerosis in ApoE-/- mice induced by angiotensin II through FAK-Akt-mTOR-NF-kappaB signaling pathway.

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.

• Authors: Yixi Chen, Jianping Cao, Qihui Zhao, Haiyong Luo, Yiguang Wang, Wenjian Dai
• Journal: The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology (Korean J Physiol Pharmacol) Vol. 22 Issue 2 Pg. 127-134 (Mar 2018) ISSN: 1226-4512 [Print] Korea (South)
• PMID: 29520165 (Publication Type: Journal Article)