title: Adenovirus-mediated gene transfer of superoxide dismutase and catalase decreases restenosis after balloon angioplasty.
abstract: BACKGROUND
  Reactive oxygen species (ROS) production increases after injury and potentially contributes to restenosis after angioplasty. We therefore evaluated the effect of adenovirus-mediated gene transfer (Ad) of superoxide dismutase (SOD) and catalase (CAT) on ROS production and restenosis after balloon angioplasty.
  
  
  METHODS
  O(2)(-) and H(2)O(2 )production was quantified in cultured cells after incubation with either LPS or CuSO(4). Angioplasty and gene transfer were performed in rabbit atherosclerotic iliac arteries. One artery was injected with AdSOD and AdCAT, while the contralateral artery was injected with an adenovirus carrying no transgene, and served as control.
  
  
  RESULTS
  ROS production was significantly decreased after adenovirus-mediated gene transfer of SOD and CAT as compared with control. Treated arteries showed less restenosis (32 +/- 27 vs. 63 +/- 19%, p = 0.003) and less constrictive remodeling (1.2 +/- 0.3 vs. 0.9 +/- 0.2, p = 0.02) than control arteries. Arteries injected with AdSOD and AdCAT showed better vasoreactivity to acetylcholine (11 +/- 4 vs. -1 +/- 6%, p < 0.05), lower collagen density (43 +/- 16 vs. 53 +/- 23%, p = 0.03), and lower inflammatory cell infiltration (22 +/- 6 vs. 36 +/- 11%, p = 0.04) than control arteries.
  
  
  CONCLUSIONS
  Our data suggest that adenovirus-mediated gene transfer of SOD and CAT reduced oxidative stress, restenosis, collagen accumulation, and inflammation and improved endothelial function after angioplasty.
authors.affiliation: European Georges Pompidou Hospital, AP-HP, INSERM E00-16, Faculté de Médecine Paris V, Université René Descartes, 20 rue Leblanc, FR-75340 Paris Cedex 07, France. durand@necker.fr
authors.forename: Eric
authors.initials: E
authors.lastname: Durand
authors.forename: Ayman
authors.initials: A
authors.lastname: Al Haj Zen
authors.forename: Faouzi
authors.initials: F
authors.lastname: Addad
authors.forename: Camille
authors.initials: C
authors.lastname: Brasselet
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Caligiuri
authors.forename: François
authors.initials: F
authors.lastname: Vinchon
authors.forename: Patricia
authors.initials: P
authors.lastname: Lemarchand
authors.forename: Michel
authors.initials: M
authors.lastname: Desnos
authors.forename: Patrick
authors.initials: P
authors.lastname: Bruneval
authors.forename: Antoine
authors.initials: A
authors.lastname: Lafont
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000800:Angioplasty, Balloon; D000818:Animals; D001011:Aorta / Q000378:metabolism; D001161:Arteriosclerosis / Q000628:therapy*; D002374:Catalase / Q000235:genetics*; D002478:Cells, Cultured; D003094:Collagen / Q000037:antagonists & inhibitors; D004730:Endothelium, Vascular / Q000503:physiopathology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D007083:Iliac Artery / Q000378:metabolism / Q000503:physiopathology; D007249:Inflammation / Q000517:prevention & control; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D018384:Oxidative Stress; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors; D055502:Secondary Prevention; D013482:Superoxide Dismutase / Q000235:genetics*
chemical_list: D017382:Reactive Oxygen Species; D003094:Collagen; D002374:Catalase; D013482:Superoxide Dismutase