Local resistance to oxidative stress by overexpression of copper-zinc superoxide dismutase limits neointimal formation after angioplasty.
OBJECTIVE
To examine the effects of oxidative stress on neointimal hyperplasia through local overexpression of human copper-zinc superoxide dismutase (Cu-Zn SOD).


METHODS
The left common femoral arteries (CFA) of 18 New Zealand white rabbits were subjected to balloon overdilation injury. Each dilated CFA was then incubated with either a nonviral (buffer) or viral (adenovirus overexpressing beta-galactosidase) control or an adenovirus overexpressing Cu-Zn SOD. Animals were then sacrificed at 3, 7, or 28 days (3 arteries per group per time point) and the treated CFA segments were harvested for analysis of esterase-positive inflammatory cells and extracellular matrix elements. The intima-to-media ratio (I/M) was measured to assess the degree of neointimal formation.


RESULTS
At 3 days, local SOD levels in the Cu-Zn SOD-treated group were significantly elevated relative to both controls (p<0.01). Significant reductions in lipid peroxidation byproducts were also seen in the SOD group relative to viral and nonviral controls (p<0.05). Mean I/M at 28 days was 0.582+/-0.088 for the nonviral control group versus 0.565+/-0.133 for the viral control group. The SOD-treated group had a significant reduction relative to both controls: 0.259+/-0.045 (p<0.05). Statistically significant reductions in I/M were also demonstrated in the SOD group relative to control groups at 7 days (p<0.05). The SOD-treated group demonstrated significant preservation of elastin relative to controls, as well as a significant reduction in esterase-positive granulocytes relative to controls (p<0.05).


CONCLUSIONS
Direct buffering of oxidative stress in balloon-injured vessels can significantly alter postinjury response and limit neointimal hyperplasia.
Kuo
Michael D
MD
Division of Cardiovascular and Interventional Radiology, Stanford University School of Medicine, Stanford, California, USA. mkuo@ucsd.edu
Bright
Isaac J
IJ
Wang
David S
DS
Ghafouri
Paras
P
Yuksel
Eser
E
Hilfiker
Paul R
PR
Miniati
Douglas N
DN
Dake
Michael D
MD
D000800:Angioplasty, Balloon / Q000009:adverse effects / Q000379:methods; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001707:Biopsy, Needle; D004195:Disease Models, Animal; D005260:Female; D005263:Femoral Artery / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D018384:Oxidative Stress / Q000502:physiology*; D011336:Probability; D011897:Random Allocation; D012016:Reference Values; D015427:Reperfusion Injury / Q000175:diagnosis*; D012680:Sensitivity and Specificity; D013482:Superoxide Dismutase / Q000378:metabolism*; D020858:Tissue and Organ Harvesting; D017539:Tunica Intima / Q000473:pathology*; D014655:Vascular Resistance
D015415:Biomarkers; D013482:Superoxide Dismutase