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Micro RNA ‐214‐3p: A link between autophagy and endothelial cell dysfunction in atherosclerosis

2017; Wiley; Volume: 222; Issue: 3 Linguagem: Inglês

10.1111/apha.12973

1748-1716

J. Wang, Wenjie Wang, Shufeng Xu, Hong Wu, Bing Dai, Dan Jian, Mei Yang, Yifu Wu, Qiang Feng, Jianhua Zhu, Longhui Zhang, Longhui Zhang,

MicroRNA in disease regulation

Abstract Aim Endothelial cell injury assumes a fundamental part in the pathogenesis of atherosclerosis, and endothelial cell autophagy has protective effects on the development of atherosclerosis, although the underlying molecular regulation mechanism is indistinct. This study aimed to investigate whether micro RNA ‐214‐3p (miR‐214‐3p) is involved in the endothelial cell autophagy regulation of atherosclerosis. Methods We utilized ApoE −/− mice provided with a high‐fat diet ( HFD ) as atherosclerosis model. We analysed the level of miR‐214‐3p and the levels of autophagy‐related protein 5 ( ATG 5) and autophagy‐related protein 12 ( ATG 12) in the purified CD 31 + endothelial cells from mouse aorta. Bioinformatics analysis and a dual‐luciferase reporter assay were performed to confirm the binding target of miR‐214‐3p. In vitro study, human umbilical vein endothelial cells ( HUVEC s) were transfected with miR‐214‐3p mimics/inhibitor and stimulated with 100 μg/mL oxidized low‐density lipoprotein (ox‐ LDL ) for 12 hours to initiate a stress‐repairing autophagic process. Results In mouse models, we identified an inverse correlation between miR‐214‐3p, ATG 5 and ATG 12. We observed that in young HUVEC s, ox‐ LDL ‐initiated autophagy was repressed by miR‐214‐3p overexpression, as evaluated by autophagic protein analysis, microtubule‐associated protein 1 light chain 3B‐ II ( LC 3B‐ II ) immunofluorescence assay and transmission electron microscopy ( TEM ). Also, miR‐214‐3p promoted ox‐ LDL accumulation in HUVEC s and THP ‐1 monocyte adhesion. Conversely, in old HUVEC s, suppression of miR‐214‐3p preserved the ability to initiate a protective autophagy reaction to the ox‐ LDL stimulation. Conclusion miR‐214‐3p regulates ox‐ LDL ‐initiated autophagy in HUVEC s by directly targeting the 3′ UTR of ATG 5 and may have a suitable role in the pathogenesis of atherosclerosis.