Abstract
Objective
To propose and verify a hypothesis that miR-17-5p knockdown may mitigate atherosclerotic lesions using atherosclerotic ApoE−/− mice as serum microRNA-17-5p (miR-17-5p) is elevated in patients with atherosclerosis.
Results
The level of miR-17-5p was higher while the level of very low density lipoprotein receptor (VLDLR), a predicted target of miR-17-5p, was lower in the peripheral blood lymphocytes (PBLs) of atherosclerosis patients as compared with control PBLs. ApoE−/− mice fed with a high-cholesterol diet displayed marked atherosclerotic vascular lesions, which were ameliorated after treatment with antagomiR-17-5p. Moreover, the decreased VLDLR in atherosclerotic mice was partly restored when miR-17-5p was antagonized. Further, luciferase assay confirmed VLDLR as a direct target of miR-17-5p in vascular smooth muscle cells (VSMCs). In addition, the elevated expression of proprotein convertase subtilisin kexin 9 (PCSK9), a secreted protease that binds to and promotes VLDLR degradation, in the atherosclerotic mice was suppressed by antagomiR-17-5p.
Conclusions
A novel interaction between miR-17-5p and VLDLR is revealed and suggests that miR-17-5p may be a potential therapeutic target for AS.
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Supporting information
Supplementary Table 1—Primer information used for RT-PCR analysis.
Supplementary Figure 1—The expression level of VLDLR after treatment with or without antagomiR-17-5p in the heart of atherosclerotic ApoE−/− mice by Western blot analysis.
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Tan, L., Meng, L., Shi, X. et al. Knockdown of microRNA-17-5p ameliorates atherosclerotic lesions in ApoE−/− mice and restores the expression of very low density lipoprotein receptor. Biotechnol Lett 39, 967–976 (2017). https://doi.org/10.1007/s10529-017-2337-y
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DOI: https://doi.org/10.1007/s10529-017-2337-y