TY - JOUR
T1 - Gene transfer of superoxide dismutase isoforms reverses endothelial dysfunction in diabetic rabbit aorta
AU - Zanetti, Michela
AU - Sato, Jun'ichi
AU - Katusic, Zvonimir S.
AU - O'Brien, Timothy
PY - 2001
Y1 - 2001
N2 - Increased production of oxygen free radicals is an important mechanism of endothelial dysfunction in diabetes mellitus. Our goal was to test whether adenovirus (Ad)-mediated gene transfer of copper/zinc (CuZn) or manganese superoxide dismutase (Mn SOD) improves relaxation of diabetic vessels. The aortas from 9 alloxan-induced diabetic mellitus (DM) and 16 control rabbits were used. Control and DM rings were transduced ex vivo with Ad vectors encoding Mn SOD (AdMn SOD), CuZn SOD (AdCuZn SOD), β-galactosidase (Adβgal), or diluents. In the absence of gene transfer, SOD activity was significantly increased in DM aortas. Transgene expression in DM AdCuZn SOD and DM AdMn SOD-transduced vessels was confirmed by Western blot analysis and by increased SOD activity (DM AdCuZn SOD, 76.2 ± 9.3; DM AdMn SOD, 65.2 ± 4.8; P < 0.05 vs. DM Adβgal; 50.9 ± 4.4 U/mg protein). Superoxide production was increased in DM Adβgal-transduced aorta and relaxations to acetylcholine were impaired in these vessels. Gene transfer of CuZn SOD and Mn SOD corrected both of these defects. Thus Ad-mediated gene transfer CuZn and Mn SOD to the diabetic aorta improves endothelium-dependent relaxation.
AB - Increased production of oxygen free radicals is an important mechanism of endothelial dysfunction in diabetes mellitus. Our goal was to test whether adenovirus (Ad)-mediated gene transfer of copper/zinc (CuZn) or manganese superoxide dismutase (Mn SOD) improves relaxation of diabetic vessels. The aortas from 9 alloxan-induced diabetic mellitus (DM) and 16 control rabbits were used. Control and DM rings were transduced ex vivo with Ad vectors encoding Mn SOD (AdMn SOD), CuZn SOD (AdCuZn SOD), β-galactosidase (Adβgal), or diluents. In the absence of gene transfer, SOD activity was significantly increased in DM aortas. Transgene expression in DM AdCuZn SOD and DM AdMn SOD-transduced vessels was confirmed by Western blot analysis and by increased SOD activity (DM AdCuZn SOD, 76.2 ± 9.3; DM AdMn SOD, 65.2 ± 4.8; P < 0.05 vs. DM Adβgal; 50.9 ± 4.4 U/mg protein). Superoxide production was increased in DM Adβgal-transduced aorta and relaxations to acetylcholine were impaired in these vessels. Gene transfer of CuZn SOD and Mn SOD corrected both of these defects. Thus Ad-mediated gene transfer CuZn and Mn SOD to the diabetic aorta improves endothelium-dependent relaxation.
KW - Adenoviral vector
KW - Diabetes mellitus
KW - Endothelium
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U2 - 10.1152/ajpheart.2001.280.6.h2516
DO - 10.1152/ajpheart.2001.280.6.h2516
M3 - Article
C2 - 11356606
AN - SCOPUS:0034987628
SN - 0363-6135
VL - 280
SP - H2516-H2523
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 6 49-6
ER -