title: Extracellular superoxide dismutase overexpression reduces cuff-induced arterial neointimal formation.
abstract: The mechanisms of neointimal formation in cuff-injury models are still uncertain. To examine whether extracellular superoxide dismutase (EC-SOD) can reduce neointimal formation in a cuff-injury model, adenoviruses expressing EC-SOD (AxCAEC-SOD) or Escherichia coli beta-galactosidase (AxCALacZ) was injected between the cuff and the adventitia of rat femoral arteries. As a result, EC-SOD protein was effectively produced in the adventitia, as assessed by immunohistochemical staining. In comparison with cuff-treated control arteries and AxCALacZ-transfected arteries, neointimal formation was significantly reduced in AxCAEC-SOD-transfected arteries. Furthermore, proliferating smooth muscle cells in neointima and media were reduced by EC-SOD treatment. Similarly, augmented iNOS expression, apoptosis and collagen content in the vascular wall were also reduced by EC-SOD treatment. Reactive oxygen species (ROS) generation in tissue was reduced by EC-SOD expression, as assessed by dihydroethidium staining and coelenterazine chemiluminescence. These results suggest that ROS, especially superoxide anions at an adventitia, are responsible for neointimal formation in a cuff-injury model.
authors.affiliation: Second Department of Internal Medicine, University of Occupational and Environmental Health, Yahatanishiku, Kitakyushu, Japan.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ozumi
authors.forename: Hiromi
authors.initials: H
authors.lastname: Tasaki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takatsu
authors.forename: Sei
authors.initials: S
authors.lastname: Nakata
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Morishita
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Koide
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Yamashita
authors.forename: Masato
authors.initials: M
authors.lastname: Tsutsui
authors.forename: Masahiro
authors.initials: M
authors.lastname: Okazaki
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Sasaguri
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Adachi
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Nakashima
mesh_terms: D000818:Animals; D017209:Apoptosis; D003094:Collagen / Q000378:metabolism; D003250:Constriction; D005263:Femoral Artery / Q000293:injuries* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000378:metabolism*; D017539:Tunica Intima / Q000503:physiopathology*; D014947:Wounds and Injuries / Q000201:enzymology / Q000378:metabolism / Q000503:physiopathology
chemical_list: D003094:Collagen; C499089:Sod3 protein, rat; D013482:Superoxide Dismutase