title: DNA enzyme ED5 depletes egr-1 and inhibits neointimal hyperplasia in rats.
abstract: OBJECTIVE
  Depletion of early growth response factor-1 (Egr-1) by a DNA enzyme, ED5, inhibits neointimal hyperplasia (NH) following vascular injury by an unknown mechanism. The aim of this study was to characterize the effects of ED5 in a rat carotid injury model in order to elucidate the mechanism by which ED5 inhibits NH.
  
  
  METHODS
  ED5 was transfected into the arterial wall of Wistar rats using FuGENE6 transfection reagent following artery balloon injury. Hematoxylin and eosin staining, immunohistochemistry, real-time reverse transcription polymerase chain reaction and Western blotting analysis were used to characterize the response to ED5.
  
  
  RESULTS
  NH decreased significantly in the ED5- plus FuGENE6-treated rats (p < 0.05) compared with the control groups, and this was accompanied by a reduced inflammatory response. Egr-1 mRNA and protein levels were significantly decreased in the ED5-treated group, as expected. The decrease in Egr-1 was accompanied by decreases in the mRNA and protein levels of PDGF-BB, Cyclin D1, CDK4, MCP-1, and ICAM-1 (p < 0.05).
  
  
  CONCLUSIONS
  Transfection of the Egr-1-specific synthetic DNA enzyme ED5 significantly reduced NH after injury in rats, at least in part, as a result of decreased expression of downstream proliferative genes such as PDGF-BB, Cyclin D1, CDK4, and the inflammatory factors MCP-1 and ICAM-1.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, China.
authors.forename: Tai-Ran
authors.initials: TR
authors.lastname: Wang
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.forename: Gui-Nan
authors.initials: GN
authors.lastname: Liu
mesh_terms: D000818:Animals; D000077214:Becaplermin; D002339:Carotid Arteries / Q000473:pathology*; D020212:Carotid Artery Injuries / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019938:Cyclin D1 / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000008:administration & dosage*; D051766:Early Growth Response Protein 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006965:Hyperplasia / Q000517:prevention & control; D008297:Male; D058426:Neointima / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D020574:Proto-Oncogene Proteins c-sis / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
chemical_list: C400152:DNA enzyme ED5; D004277:DNA, Single-Stranded; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D020574:Proto-Oncogene Proteins c-sis; D019938:Cyclin D1; D000077214:Becaplermin