Lili Tan1, Liang Meng2, Xiaojing Shi3, Bo Yu4. 1. Department of Cardiology, The First Affiliated Hospital of China Medical University, 155 North Nanjing Street, Shenyang, 110001, Liaoning, People's Republic of China. 2. Department of Cardiology, Central Hospital Affiliated to Shenyang Medical College, Shenyang, 110024, Liaoning, People's Republic of China. 3. Department of Cardiology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121001, Liaoning, People's Republic of China. 4. Department of Cardiology, The First Affiliated Hospital of China Medical University, 155 North Nanjing Street, Shenyang, 110001, Liaoning, People's Republic of China. ybydyxls@163.com.
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.
OBJECTIVE: To propose and verify a hypothesis that miR-17-5p knockdown may mitigate atherosclerotic lesions using atheroscleroticApoE-/- miceas 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 atherosclerosispatientsas 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 atheroscleroticmice was partly restored when miR-17-5p was antagonized. Further, luciferase assay confirmed VLDLRas 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 atheroscleroticmice 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.
Entities:
Keywords:
Atherosclerosis; MicroRNA-17-5p; Proprotein convertase subtilisin kexin 9; Very low density lipoprotein receptor