title: Deficiency of CuZn superoxide dismutase promotes inflammation and alters medial structure following vascular injury.
abstract: OBJECTIVE
  The anti-oxidant enzyme copper/zinc superoxide dismutase (CuZnSOD) metabolizes superoxide anion (O(2)(-)) in vascular cells. However, the role of CuZnSOD in vascular injury remains poorly understood.
  
  
  METHODS
  Using CuZnSOD-deficient (CuZnSOD(-/-)) mice and wild-type (WT) mice, we investigated morphometric changes and the role of O(2)(-) in vascular remodeling after femoral artery injury induced by an external vascular cuff model.
  
  
  RESULTS
  Three days post-injury, inflammatory cell infiltration increased significantly. Moreover, the percent positive area of tumor necrosis factor-α (TNF-α), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) in media were higher in CuZnSOD(-/-) mice than in WT mice (TNF-α: 34.8±8.4% versus 18.8±5.6%, p < 0.05, ICAM-1: 29.6±6.5% versus 11.0±2.8%, p < 0.05, VCAM-1: 23.5±7.5% versus 3.7±1.1%, p < 0.05). mRNA expression of iNOS was markedly increased in CuZnSOD(-/-) mice with cuff injury. Dihydroethidine staining revealed increased levels of vascular O(2)(-) in media from CuZnSOD(-/-) mice. Although neointimal formation remained unchanged, 14 days postinjury, we observed degeneration of the media, and the media/vessel wall ratio increased in CuZnSOD(-/-) mice (40.4±2.1% versus 26.8±1.4%, p < 0.05). Furthermore, SMemb/MHC-B-stained lesions increased markedly in CuZnSOD(-/-) mice.
  
  
  CONCLUSIONS
  CuZnSOD-deficiency promoted inflammation, expressed adhesion molecules, and altered the structure of the media post-injury. Our results suggest that O(2)(-) participates importantly in the progression of early stage vascular inflammation, resulting in vascular remodeling in media but not neointimal formation, post-injury.
authors.affiliation: Department of Internal Medicine 1, National Defense Medical College, Saitama, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Ishigami
authors.forename: Kikuo
authors.initials: K
authors.lastname: Isoda
authors.forename: Takeshi
authors.initials: T
authors.lastname: Adachi
authors.forename: Tomiharu
authors.initials: T
authors.lastname: Niida
authors.forename: Takehiko
authors.initials: T
authors.lastname: Kujiraoka
authors.forename: Daihiko
authors.initials: D
authors.lastname: Hakuno
authors.forename: Harumi
authors.initials: H
authors.lastname: Kondo
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kusuhara
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Ohsuzu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D005260:Female; D005263:Femoral Artery / Q000201:enzymology / Q000293:injuries*; D007124:Immunoenzyme Techniques; D007249:Inflammation / Q000201:enzymology / Q000209:etiology / Q000473:pathology*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058426:Neointima; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000378:metabolism*; D013481:Superoxides / Q000009:adverse effects*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D057772:Vascular System Injuries / Q000150:complications* / Q000201:enzymology
chemical_list: D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D013481:Superoxides; D018799:Intercellular Adhesion Molecule-1; D052247:Nitric Oxide Synthase Type II; D013482:Superoxide Dismutase