title: Small interfering RNA to c-myc inhibits vein graft restenosis in a rat vein graft model.
abstract: BACKGROUND
  Vascular smooth muscle cell (VSMC) proliferation plays an important role in the failure of autologous vein grafts. The c-myc gene activation is highly involved in the VSMC proliferation. In this study, we made an attempt to determine whether VSMC proliferation and vein graft restenosis could be attenuated by silencing the c-myc gene with small interference RNA (siRNA).
  
  
  METHODS
  The effects of c-myc siRNA on VSMCs in vitro were examined both in cell proliferation and c-myc expression. Thirty-two Sprague-Dawley rats underwent autologous jugular vein to carotid artery reverse interposition grafting and were randomly divided in to four groups. Vein grafts were treated with pluronic gel or gel containing a scrambled siRNA or c-myc siRNA and the control group received no treatment. Intimal thickness of the vein grafts was evaluated at 3 wk after the surgery.
  
  
  RESULTS
  In vitro, c-myc siRNA inhibited cell proliferation by 40%, reduced c-myc mRNA level by 70%, and c-myc protein level by 50% compared with the controls. In vivo, the c-myc siRNA treatment reduced intimal hyperplasia by 75%.
  
  
  CONCLUSIONS
  Our data suggested that c-myc siRNA, when given immediately after the surgery, is an effective approach for the prevention of vein graft restenosis.
authors.affiliation: Department of Cardiothoracic Surgery, Jinling Hospital, Clinical Medicine School of Nanjing University, Nanjing, Jiangsu Province, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Kun
authors.initials: K
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Shen
authors.forename: Haiwei
authors.initials: H
authors.lastname: Wu
authors.forename: Hua
authors.initials: H
authors.lastname: Jing
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D006083:Graft Occlusion, Vascular / Q000517:prevention & control*; D006965:Hyperplasia / Q000517:prevention & control; D007601:Jugular Veins / Q000637:transplantation*; D008297:Male; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors* / Q000235:genetics*; D034741:RNA, Small Interfering / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016896:Treatment Outcome; D017539:Tunica Intima / Q000473:pathology
chemical_list: D016271:Proto-Oncogene Proteins c-myc; D034741:RNA, Small Interfering