MiR-590-5p Inhibits Oxidized-LDL Induced Angiogenesis by Targeting LOX-1

被引:37
作者
Dai, Yao [1 ,2 ,3 ,4 ]
Zhang, Zhigao [4 ]
Cao, Yongxiang [4 ]
Mehta, Jawahar L. [2 ,3 ]
Li, Jun [1 ]
机构
[1] Anhui Med Univ, Sch Pharm, Hefei 230032, Anhui, Peoples R China
[2] Cent Arkansas Vet Healthcare Syst, Dept Med, Little Rock, AR 72205 USA
[3] Univ Arkansas Med Sci, Little Rock, AR 72205 USA
[4] Anhui Med Univ, Affiliated Hosp 1, Dept Internal Med, Hefei 230022, Anhui, Peoples R China
基金
中国国家自然科学基金;
关键词
CELLS; MODULATION; ASPIRIN;
D O I
10.1038/srep22607
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Oxidized low-density lipoprotein (ox-LDL) is, at least in part, responsible for angiogenesis in atherosclerotic regions. This effect of ox-LDL has been shown to be mediated through a specific receptor LOX-1. Here we describe the effect of miR-590-5p on ox-LDL-mediated angiogenesis in in vitro and in vivo settings. Human umbilical vein endothelial cells (HUVECs) were transfected with miR-590-5p mimic or inhibitor followed by treatment with ox-LDL. In other experiments, Marigel plugs were inserted in the mice subcutaneous space. Both in vitro and in vivo studies showed that miR-590-5p mimic (100 nM) inhibited the ox-LDL-mediated angiogenesis (capillary tube formation, cell proliferation and migration as well as pro-angiogenic signals-ROS, MAPKs, pro-inflammatory cytokines and adhesion-related proteins). Of note, miR-590-5p inhibitor (200 nM) had the opposite effects. The inhibitory effect of miR-590-5p on angiogenesis was mediated by inhibition of LOX-1 at translational level. The inhibition of LOX-1 by miR-590-5p was confirmed by luciferase assay. In conclusion, we show that MiR-590-5p inhibits angiogenesis by targeting LOX-1 and suppressing redox-sensitive signals.
引用
收藏
页数:9
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