title: Early growth response gene-1 decoy oligonucleotides inhibit vascular smooth muscle cell proliferation and neointimal hyperplasia of autogenous vein graft in rabbits.
abstract: OBJECTIVE
  The excess proliferation of vascular smooth muscle cells (VSMCs) and the development of intimal hyperplasia is a hallmark of vein graft failure. This study aimed to verify that a single intraoperative transfection of early growth response gene-1 (Egr-1) decoy oligonucleotide (ODN) can suppress vein graft proliferation of VSMCs and intimal hyperplasia.
  
  
  METHODS
  In a rabbit model, jugular veins were treated with Egr-1 decoy ODN, scrambled decoy ODN, Fugene6, or were left untreated, then grafted to the carotid artery. The vein graft samples were obtained 48 h, 1, 2 or 3 weeks after surgery. The thickness of the intima and intima/media ratio in the grafts was analysed by haematoxylin-eosin (HE) staining. The expression of the Egr-1 decoy ODN transfected in the vein was analysed using fluorescent microscopy. Egr-1 mRNA was measured using reverse transcription-polymerase chain reaction. The expression of Egr-1 protein was analysed by Western blot and immunohistochemistry.
  
  
  RESULTS
  Transfection efficiency of the ODN was confirmed by 4', 6-diamidino-2-phenylindole staining. In the grafts treated with Egr-1 decoy ODN, our study achieved statistically significant inhibition of intimal hyperplasia by ∼58% at 3 weeks. Transfection of Egr-1 decoy ODNs decreased the protein expression of Egr-1 and Egr-1 mRNA.
  
  
  CONCLUSIONS
  We confirmed that gene therapy using in vivo transfection of an Egr-1 decoy ODN significantly inhibits proliferation of VSMC and intimal hyperplasia of vein grafts in a rabbit model.
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Tongji Hospital of Tongji University, Shanghai, China.
authors.forename: Xisheng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Tongji Hospital of Tongji University, Shanghai, China rabbitmei2000@yahoo.com.cn.
authors.forename: Yunqing
authors.initials: Y
authors.lastname: Mei
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Tongji Hospital of Tongji University, Shanghai, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ji
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Tongji Hospital of Tongji University, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Tongji Hospital of Tongji University, Shanghai, China.
authors.forename: Jianzhi
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Tongji Hospital of Tongji University, Shanghai, China.
authors.forename: Shiliang
authors.initials: S
authors.lastname: Xie
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D004195:Disease Models, Animal; D015536:Down-Regulation; D051766:Early Growth Response Protein 1 / Q000235:genetics / Q000378:metabolism*; D015316:Genetic Therapy / Q000379:methods*; D006083:Graft Occlusion, Vascular / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D006965:Hyperplasia; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D058426:Neointima; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D012501:Saphenous Vein / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
chemical_list: D051766:Early Growth Response Protein 1; D009841:Oligonucleotides; D012333:RNA, Messenger
keywords: Decoy; Early growth response gene-1; Gene therapy; Intimal hyperplasia