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

• 발행기관: 대한생리학회-대한약리학회
• 저자명: Yixi Chen Jianping Cao Qihui Zhao Haiyong Luo Yiguang Wang Wenjian Dai
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제22권 제2호, 127~134쪽, 전체 8쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2018.03.31

영문 초록

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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INTRODUCTION

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키워드

Angiotensin II Apolipoprotein E Atherosclerosis Myofibrillogenesis regulator-1 NF-κB siRNA