title: Upregulation of let-7a inhibits vascular smooth muscle cell proliferation in vitro and in vein graft intimal hyperplasia in rats.
abstract: BACKGROUND
  Proliferation of vascular smooth muscle cells (VSMCs) is a crucial event in the pathogenesis of intimal hyperplasia, which is the main cause of restenosis after vascular reconstruction. In this study, we assessed the impact of let-7a microRNA (miRNA) on the proliferation of VSMCs.
  
  
  METHODS
  Using miRNA microarrays analysis for miRNA expression in the vein graft model. Lentiviral vector-mediated let-7a was transfected into the vein grafts. In situ hybridization was performed to detect let-7a. Cultured rat VSMCs were transfected with let-7a mimics for different periods of time. Cell proliferation, migration and cell cycle activity were monitored following transfection of the let-7a mimics. Immunohistochemical and Western blotting analysis the expression levels of c-myc and K-ras.
  
  
  RESULTS
  We found that let-7a was the most downregulated miRNA in the vein graft model. In vivo proliferation of VSMCs was assessed in a rat model of venous graft intimal hyperplasia. Let-7a was found to localize mainly to the VSMCs. Let-7a miRNA expression was increased in VSMCs in the neointima of the let-7a treated group. Intimal hyperplasia was suppressed by upregulation of let-7a via lentiviral vector-mediated mimics. In cultured VSMCs, the expression of let-7a increased upon starving, and the upregulation of let-7a miRNA significantly decreased cell proliferation and migration. Immunohistochemical and Western blotting analysis demonstrated that treatment with let-7a mimics resulted in decreased expression levels of c-myc and K-ras.
  
  
  CONCLUSIONS
  The results indicate that let-7a miRNA is a novel regulator of VSMC proliferation in intimal hyperplasia. These findings suggest that let-7a miRNA is a promising therapeutic target for the prevention of intimal hyperplasia.
authors: Department of Vascular Surgery, The First Affiliated Hospital, China Medical University, Shenyang, China.
authors: Hui
authors: H
authors: Cao
authors: Department of Vascular Surgery, The First Affiliated Hospital, China Medical University, Shenyang, China. Electronic address: xhhu@mail.cmu.edu.cn.
authors: Xinhua
authors: X
authors: Hu
authors: Department of Vascular Surgery, The First Affiliated Hospital, China Medical University, Shenyang, China.
authors: Qiang
authors: Q
authors: Zhang
authors: Department of Vascular Surgery, The First Affiliated Hospital, China Medical University, Shenyang, China.
authors: Junpeng
authors: J
authors: Wang
authors: Department of Vascular Surgery, The First Affiliated Hospital, China Medical University, Shenyang, China.
authors: Jun
authors: J
authors: Li
authors: Department of Vascular Surgery, The First Affiliated Hospital, China Medical University, Shenyang, China.
authors: Bing
authors: B
authors: Liu
authors: Department of Vascular Surgery, The First Affiliated Hospital, China Medical University, Shenyang, China.
authors: Yang
authors: Y
authors: Shao
authors: Department of Vascular Surgery, The First Affiliated Hospital, China Medical University, Shenyang, China.
authors: Xi
authors: X
authors: Li
authors: Department of Vascular Surgery, The First Affiliated Hospital, China Medical University, Shenyang, China.
authors: Jian
authors: J
authors: Zhang
authors: Department of Vascular Surgery, The First Affiliated Hospital, China Medical University, Shenyang, China.
authors: Shijie
authors: S
authors: Xin
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D016259:Genes, myc / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D006083:Graft Occlusion, Vascular / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D006085:Graft Survival / Q000187:drug effects / Q000502:physiology; D007601:Jugular Veins / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D017539:Tunica Intima / Q000166:cytology / Q000502:physiology; D015854:Up-Regulation / Q000502:physiology
chemical_list: C548145:MIRNLET7 microRNA, rat; D035683:MicroRNAs; D010982:Platelet-Derived Growth Factor
keywords: Intimal hyperplasia; Let-7a; Proliferation; Vascular smooth muscle cells; Vein graft