Journal
CELLULAR & MOLECULAR BIOLOGY LETTERS
Volume 22, Issue -, Pages 1-13Publisher
BMC
DOI: 10.1186/s11658-017-0033-5
Keywords
Atherosclerosis; miR-210; PDK1; Endothelial cell apoptosis; ApoE (-/-)
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Background: Atherosclerosis is a chronically inflammatory disease and one of the leading causes of deaths worldwide. Endothelial cell apoptosis plays a crucial role in its development. Several microRNAs (miRNAs) are reportedly involved in atherosclerotic plaque formation, including miRNA-210 (miR-210). However, the underlying mechanism of its role in endothelial cell apoptosis during atherosclerosis is still largely unknown. Methods: A mouse model with atherosclerosis induced by a high-fat diet (HFD) was built in ApoE (-/-) mice. The levels of endothelial cell apoptosis were determined via flow cytometry. The expressions of miR-210 and PDK1 in purified CD31+ endothelial cells from mouse aorta were measured via RT-qPCR and western blot. Binding between miR-210 and the 3'-untranslated region (UTR) of PDK1 mRNA was predicted using bioinformatics analyses and confirmed with a dual luciferase reporter assay. The effects of miR-210 were further analyzed in an in vitro model using human aortic endothelial cells (HAECs) treated with oxidized low-density lipoprotein (ox-LDL). Results: We found that the HFD mice developed atherosclerosis in 12 weeks and had a significantly higher percentage of endothelial cell apoptosis. The upregulated level of miR-210 in the HFD mice and HAECs inversely correlated with the level of PDK1. Inhibiting miR-210 expression significantly reduced HAEC apoptosis, as evidenced by the results of the MTT and flow cytometry experiments. Further analysis identified PDK1 as the target of miR-210 and showed that PDK1 overexpression reversed the proapoptotic effect of miR-210 through mediation of the P13K/Akt/mTOR pathways. Conclusion: Our study suggests a novel role for miR-210 in the progression of atherosclerosis through the regulation of endothelial apoptosis. This indicates that miR-210 might have potential in treatment of atherosclerosis.
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