Extracellular superoxide dismutase overexpression reduces cuff-induced arterial neointimal formation.
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.
Ozumi
Kiyoshi
K
Second Department of Internal Medicine, University of Occupational and Environmental Health, Yahatanishiku, Kitakyushu, Japan.
Tasaki
Hiromi
H
Takatsu
Hiroyuki
H
Nakata
Sei
S
Morishita
Tsuyoshi
T
Koide
Shinichiro
S
Yamashita
Kazuhito
K
Tsutsui
Masato
M
Okazaki
Masahiro
M
Sasaguri
Yasuyuki
Y
Adachi
Tetsuo
T
Nakashima
Yasuhide
Y
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
D003094:Collagen; C499089:Sod3 protein, rat; D013482:Superoxide Dismutase