TY - JOUR
T1 - Adenovirus-mediated gene transfer of superoxide dismutase and catalase decreases restenosis after balloon angioplasty
AU - Durand, Eric
AU - Zen, Ayman Al Haj
AU - Addad, Faouzi
AU - Brasselet, Camille
AU - Caligiuri, Giuseppina
AU - Vinchon, François
AU - Lemarchand, Patricia
AU - Desnos, Michel
AU - Bruneval, Patrick
AU - Lafont, Antoine
PY - 2005/5
Y1 - 2005/5
N2 - 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: O2- and H2O 2 production was quantified in cultured cells after incubation with either LPS or CuSO4. 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.
AB - 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: O2- and H2O 2 production was quantified in cultured cells after incubation with either LPS or CuSO4. 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.
KW - Endothelial function
KW - Extracellular matrix
KW - Gene therapy
KW - Redox signaling
KW - Restenosis
UR - http://www.scopus.com/inward/record.url?scp=22144471222&partnerID=8YFLogxK
U2 - 10.1159/000085658
DO - 10.1159/000085658
M3 - Article
C2 - 15870505
AN - SCOPUS:22144471222
SN - 1018-1172
VL - 42
SP - 255
EP - 265
JO - Journal of Vascular Research
JF - Journal of Vascular Research
IS - 3
ER -