Research Repository

Superoxide Anions and Endothelial Cell Proliferation in Normoglycemia and Hyperglycemia

Zanetti, Michela and Zwacka, Ralph M and Engelhardt, John F and Katusic, Zvonimir S and O’Brien, Timothy (2001) 'Superoxide Anions and Endothelial Cell Proliferation in Normoglycemia and Hyperglycemia.' Arteriosclerosis, Thrombosis, and Vascular Biology, 21 (2). pp. 195-200. ISSN 1079-5642

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<jats:p> <jats:italic>Abstract</jats:italic> —Oxygen free radicals are believed to play a key role in cellular proliferation, and increased concentrations of these molecules have been implicated in the pathogenesis of endothelial dysfunction in diabetes mellitus. Our aim was to study the role of superoxide anions in endothelial cell proliferation under conditions of normoglycemia and hyperglycemia. Human aortic endothelial cells (HAECs) and human umbilical vein endothelial cells (HUVECs) exposed to adenoviral vectors encoding CuZnSOD (AdCuZnSOD), β-galactosidase (Adβgal), or diluent (control) were cultured in normal glucose (NG, 5.5 mmol/L) or high glucose (HG, 28 mmol/L) medium. Cell proliferation was compared by use of [ <jats:sup>3</jats:sup> H]thymidine incorporation and cell count in transduced and control cells in the setting of NG and HG. Transgene expression was detected in transduced cells by X-gal staining and by Western analysis and SOD activity assay in AdCuZnSOD-transduced cells. Superoxide production was significantly ( <jats:italic>P</jats:italic> &lt;0.05) decreased in AdCuZnSOD-transduced cells cultured in both NG and HG medium. In NG, AdCuZnSOD-transduced endothelial cells had decreased proliferation compared with control cells. After 48 hours in HG, superoxide levels were increased and DNA synthesis was decreased ( <jats:italic>P</jats:italic> &lt;0.05) in control and Adβgal-transduced but were not affected in AdCuZnSOD-transduced cells. In addition, after 7 days in HG, cell counts were reduced ( <jats:italic>P</jats:italic> &lt;0.05) in control (73±2.5%) and Adβgal-transduced (75±3.4%) but not in AdCuZnSOD-transduced cells (89±3.4%). These results suggest that either a deficiency or an excess of superoxide anions inhibits endothelial cell proliferation, and the inhibitory effect of increased superoxide due to hyperglycemia can be reversed by CuZnSOD overexpression. </jats:p>

Item Type: Article
Uncontrolled Keywords: gene transfer; adenovirus; endothelium; diabetes mellitus; superoxide dismutase
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 29 Jun 2017 19:48
Last Modified: 15 Jan 2022 00:47

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