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Overexpression of human superoxide dismutase inhibits oxidation of low- density lipoprotein by endothelial cells

Fang, X and Weintraub, NL and Rios, CD and Chappell, DA and Zwacka, RM and Engelhardt, JF and Oberley, LW and Yan, T and Heistad, DD and Spector, AA (1998) 'Overexpression of human superoxide dismutase inhibits oxidation of low- density lipoprotein by endothelial cells.' Circulation Research, 82 (12). 1289 - 1297. ISSN 0009-7330

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Oxidation of LDL in the subendothelial space has been proposed to play a key role in atherosclerosis. Endothelial cells produce superoxide anions (O2·-) and oxidize LDL in vitro; however, the role of O2·- in endothelial cell-induced LDL oxidation is unclear. Incubation of human LDL (200/μg/mL) with bovine aortic endothelial cells (BAECs) for 18 hours resulted in a 4-fold increase in LDL oxidation compared with cell-free incubation (22.5 ± 1.1 versus 6.3±0.2 [mean±SEM] nmol malondialdehyde/mg LDL protein, respectively; P<0.05). Under similar conditions, incubation of LDL with porcine aortic endothelial cells resulted in a 5-fold increase in LDL oxidation. Inclusion of exogenous copper/zinc superoxide dismutase (Cu/ZnSOD, 100/μg/mL) in the medium reduced BAEC-induced LDL oxidation by 79%. To determine whether the intracellular SOD content can have a similar protective effect, BAECs were infected with adenoviral vectors containing cDNA for human Cu/ZnSOD (AdCu/ZnSOD) or manganese SOD (AdMnSOD). Adenoviral infection increased the content and activity of either Cu/ZnSOD or MnSOD in the cells and reduced cellular 02·- release by two thirds. When cells infected with AdCu/ZnSOD or AdMnSOD were incubated with LDL, formation of malondialdehyde was decreased by 77% and 32%, respectively. Two other indices of LDL oxidation, formation of conjugated dienes and increased LDL electrophoretic mobility, were similarly reduced by SOD transduction. These data suggest that production of 02·- contributes to endothelial cell- induced oxidation of LDL in vitro. Furthermore, adenovirus-mediated transfer of cDNA for human SOD, particularly Cu/ZnSOD, effectively reduces oxidation of LDL by endothelial cells.

Item Type: Article
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: Faculty of Science and Health > Life Sciences, School of
Depositing User: Jim Jamieson
Date Deposited: 11 Jul 2017 16:06
Last Modified: 30 Jun 2021 10:15

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