Gene transfer of superoxide dismutase isoforms reverses endothelial dysfunction in diabetic rabbit aorta

Michela Zanetti, Jun'ichi Sato, Zvonimir S. Katusic, Timothy O'Brien

Research output: Contribution to journalArticle

68 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)H2516-H2523
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume280
Issue number6 49-6
StatePublished - Jul 3 2001

Keywords

  • Adenoviral vector
  • Diabetes mellitus
  • Endothelium

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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