title: [Adenovirus-mediated transfer of TIMP-4 gene inhibits neointimal formation after balloon injury].
abstract: OBJECTIVE
  To investigate the effects of human tissue inhibitor of matelloproteinase-4 (TIMP-4) on vascular smooth muscle cells (VSMCs) migration and the neointimal formation after balloon injury in rats.
  
  
  METHODS
  The cultured VSMCs were transfected with an adenoviral vector containing human TIMP-4 gene, AdTIMP-4. Effect of TIMP-4 on VSMC migration was investigated by monolayer cell scrape. AdTIMP-4, control adenoviral vector or PBS was transduced into the rat carotid artery from the adventitial after carotid artery injury. Cell number within the internal elastic lamina 4 days after gene transfer was counted and neointima/media area ratio 28 days after gene transfer was calculated.
  
  
  RESULTS
  The migration distance of VSMCs infected with AdTIMP-4 was inhibited markedly. Morphometric analysis demonstrated a statistically significant reduction in the number of cells migrated into neointima compared with controls [(32.5 +/- 4.8) cells per section, (33.8 +/- 7.0) cells per section and (8.2 +/- 2.4) cells per section for uninfected, AdGFP-treated and AdTIMP-4-treated arteries, respectively]. There was a reduction of intima/media ratio of TIMP-4-treated group by 66.5% compared with control groups 28 days after gene transfer (P < 0.01). There was no statistical difference between the control adenoviral vector group and PBS group.
  
  
  CONCLUSIONS
  Adenoviral mediated gene transfer of TIMP-4 inhibits migration of VSMC and significantly reduces neointimal hyperplasia in the rat carotid balloon injury model. The TIMP-4 gene transfer is a potential therapeutic approach to preventing neointimal formation after balloon injury.
authors.affiliation: Department of Cardiology, Peking University First Hospital, Beijing 100034, China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Guo
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Guanghui
authors.initials: G
authors.lastname: Chen
authors.forename: Jian
authors.initials: J
authors.lastname: Tang
authors.forename: Wei
authors.initials: W
authors.lastname: Gao
mesh_terms: D000256:Adenoviridae; D000818:Animals; D002339:Carotid Arteries; D020212:Carotid Artery Injuries; D017536:Carotid Artery, Common; D002465:Cell Movement; D002478:Cells, Cultured; D004730:Endothelium, Vascular; D005822:Genetic Vectors; D006801:Humans; D006965:Hyperplasia; D009131:Muscle, Smooth, Vascular; D032389:Myocytes, Smooth Muscle; D058426:Neointima / Q000517:prevention & control*; D051381:Rats; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics*; D014162:Transfection; D017539:Tunica Intima; D017540:Tunica Media; D000097792:Tissue Inhibitor of Metalloproteinase-4
chemical_list: D019714:Tissue Inhibitor of Metalloproteinases; D000097792:Tissue Inhibitor of Metalloproteinase-4