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

Xiang Fang, Neal L. Weintraub, C. David Rios, David A. Chappell, Ralf M. Zwacka, John F. Engelhardt, Larry W. Oberley, Tao Yan, Donald D. Heistad, Arthur A. Spector

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76 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1289-1297
Number of pages9
JournalCirculation Research
Volume82
Issue number12
DOIs
StatePublished - Jun 29 1998

Keywords

  • Endothelial cell
  • Gene transfection
  • Low density lipoprotein
  • Superoxide anion
  • Superoxide dismutase

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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    Fang, X., Weintraub, N. L., Rios, C. D., Chappell, D. A., Zwacka, R. M., Engelhardt, J. F., Oberley, L. W., Yan, T., Heistad, D. D., & Spector, A. A. (1998). Overexpression of human superoxide dismutase inhibits oxidation of low- density lipoprotein by endothelial cells. Circulation Research, 82(12), 1289-1297. https://doi.org/10.1161/01.RES.82.12.1289