MicroRNA-23a-5p promotes atherosclerotic plaque progression and vulnerability by repressing ATP-binding cassette transporter A1/G1 in macrophages

作者：Yang, Shuai; Ye, Zi-ming; Chen, Shengcai; Luo, Xue-ying; Chen, Shao-li; Mao, Ling; Li, Yanan; Jin, Huijuan; Yu, Cheng; Xiang, Fei-xiang; Xie, Ming-xing; Chang, Jiang; Xia, Yuan-peng^*; Hu, Bo^*

来源：Journal of Molecular and Cellular Cardiology, 2018, 123: 139-149.

DOI：10.1016/j.yjmcc.2018.09.004

• Atherosclerosis
• miR-23a-5p
• ABCA1/ABCG1
• Foam cell formation
• Plaque vulnerability

Disruption of carotid vulnerable atherosclerotic plaque is responsible for acute ischemic stroke (MS) and the early detection and intervention approach are greatly limited. Undertaking a microarray of microRNAs (miRNAs) in the plasma of AIS patients with carotid vulnerable plaques, miR-23a-5p was markedly elevated and was positively correlated with the plaque progression and vulnerability. Correspondingly, we found that miR23a-5p expression was significantly increased in both plasma and macrophages from atherosclerosis mice. Bioinformatics analysis and in vitro knockdown experiments identified that ATP-binding cassette transporter A1/G1 as a novel target of miR-23a-5p. Luciferase reporter assays showed that miR-23a-5p repressed the 3' untranslated regions (UTR) activity of ABCA1/G1. Moreover, functional analyses demonstrated that transfection of miR-23a-5p inhibitor enhanced cholesterol efflux and decreased foam cell formation through upregulating ABCA1/G1 expression levels. Furthermore, long term in vivo systemically delivered miR-23a-5p antagomir significantly increased ABCA1/G1 expression in the aorta of ApoE(-/-) mice. Importantly, the miR-23a-5p antagomir therapy significantly reduced atherosclerosis progression and promoted plaque stability. Our observations indicate that miR-23a-5p promotes macrophage-derived foam cell formation and might be a key regulator contributing to atherosclerotic plaque progression and vulnerability.

• 出版日期2018-10
• 单位华中科技大学; 广西医科大学