Gene transfer of superoxide dismutase protects against free radical mediated impairment of vasodilation

Reactive oxygen species play an important role in mediating vascular dysfunction in disease. Gene transfer of antioxidants to blood vessels has the potential to improve vascular function. We hypothesized that gene transfer of superoxide dismutase (SOD) to vessels would protect against free radical mediated impairment of dilation. Thoracic aorta removed from New Zealand rabbits were cut into ring segments and incubated for two hours in adenovirus (5x109 pfu/ml) containing the gene for β-galactosidase, cytosolic SOD (AdCZ-SOD), extracellular SOD (AdECSOD), or no virus. After 24 hour incubation in culture media at 37°C, vessels were prepared for measurement of isometric tension in Kreb's buffer containing xanthine. After precontraction with phenylephrine, xanthine oxidase (XO) impaired relaxation to acetylcholine (Ach, max relaxation 32+4% with vs. 64+3% without XO, p<0.05, n=16) but not nitroprusside. In the presence of XO, relaxation to Ach was improved in vessels incubated with AdECSOD (47+5%, p<0.05 vs. no virus, n=10) but not AdCZSOD (33+4%). X-gal staining showed gene transfer to the endothelium and adventitia. Western blotting confirmed overexpression of both SOD isoforms. We conclude that gene transfer of ECSOD, but not CZSOD, protects against vascular dysfunction due to extracellular superoxide.

Duke Scholars

Author Francis Joseph Miller Jr. Medicine, Cardiology