title: Downregulation of quinone reductase 2 attenuates vascular smooth muscle cells proliferation and neointimal formation in balloon injured rat carotid artery.
abstract: OBJECTIVE
  Quinone reductase 2 (NQO2) is a flavoprotein that catalyzes the metabolic reduction of quinines, but its biological mechanism in vascular smooth muscle cells (VSMCs) is unclear. The aim of this study was to evaluate the role of NQO2 on VSMCs proliferation and the neointimal formation in balloon injured rat carotid artery.
  
  
  METHODS
  Left common carotid arteries from Sprague-Dawley rats were injured by a balloon catheter, and the injured arteries were incubated with 50 μL solution of NQO2-siRNA-GFP lentiviral vectors, NC-siRNA-GFP lentiviral vectors or PBS for 1 h. The rats were euthanized for morphometric and immunohistochemical analysis, real-time PCR and western blot analysis at 2 weeks after balloon injury and gene transfer. The cultured rat VSMCs transduced with NQO2-siRNA-GFP or NC-siRNA-GFP lentiviral vectors were used for cell proliferation assay, real-time PCR and western blot analysis. In order to detect the vascular or intracellular ROS level, the lentiviral vectors without GFP were used to transfect the injured common carotid arteries and the cultured rat VSMCs.
  
  
  RESULTS
  Lentiviral vectors bearing NQO2 siRNA could reduce NQO2 protein level and suppress NQO2 mRNA expression in balloon injured artery walls and cultured rat VSMCs. Downregulation of NQO2 significantly suppressed VSMCs proliferation and intimal formation. NQO2 siRNA treatment could reduce vascular or intracellular ROS level and decrease the phosphorylation of the ERK1/2 in balloon injured artery walls and cultured rat VSMCs.
  
  
  CONCLUSIONS
  Our study suggests that downregulation of NQO2 significantly suppresses VSMCs proliferation and progression of neointimal formation after vascular injury.
authors.affiliation: Department of Cardiology, Huai'an First People's Hospital affiliated to Nanjing Medical University, Huai'an, Jiangsu.
authors.forename: Xi-wen
authors.initials: XW
authors.lastname: Zhang
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.forename: Jing-bo
authors.initials: JB
authors.lastname: Cai
authors.forename: Xiao-feng
authors.initials: XF
authors.lastname: Hou
authors.forename: He-gui
authors.initials: HG
authors.lastname: Wang
authors.forename: Jian-gang
authors.initials: JG
authors.lastname: Zou
authors.forename: Ke-jiang
authors.initials: KJ
authors.lastname: Cao
mesh_terms: D000818:Animals; D015153:Blotting, Western; D020212:Carotid Artery Injuries / Q000201:enzymology / Q000473:pathology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation; D005786:Gene Expression Regulation; D005822:Genetic Vectors / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D016086:Lentivirus / Q000235:genetics; D020935:MAP Kinase Signaling System; D008297:Male; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000201:enzymology / Q000473:pathology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000201:enzymology*; D058426:Neointima / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D011808:Quinone Reductases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D049452:Green Fluorescent Proteins; C419642:NRH - quinone oxidoreductase2; D011808:Quinone Reductases