title: Knockdown of microRNA-17-5p ameliorates atherosclerotic lesions in ApoE-/-mice and restores the expression of very low density lipoprotein receptor.
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.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of China Medical University, 155 North Nanjing Street, Shenyang, 110001, Liaoning, People's Republic of China.
authors.forename: Lili
authors.initials: L
authors.lastname: Tan
authors.affiliation: Department of Cardiology, Central Hospital Affiliated to Shenyang Medical College, Shenyang, 110024, Liaoning, People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Meng
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Jinzhou Medical University, Jinzhou, 121001, Liaoning, People's Republic of China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Shi
authors.affiliation: 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.
authors.forename: Bo
authors.initials: B
authors.lastname: Yu
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000473:pathology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D055785:Gene Knockdown Techniques; D017930:Genes, Reporter; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000737:chemistry; D008156:Luciferases / Q000032:analysis; D000074085:Mice, Knockout, ApoE; D035683:MicroRNAs / Q000096:biosynthesis*; D011973:Receptors, LDL / Q000096:biosynthesis*
chemical_list: D001057:Apolipoproteins E; D035683:MicroRNAs; C543614:Mirn17 microRNA, mouse; D011973:Receptors, LDL; C036053:VLDL receptor; D008156:Luciferases
keywords: Atherosclerosis; MicroRNA-17-5p; Proprotein convertase subtilisin kexin 9; Very low density lipoprotein receptor