Reactive oxygen species have been proposed to play important roles in ather
osclerosis. To investigate the protective role of extracellular superoxide
dismutase (EC-SOD), its inhibition of endothelial-cell-mediated LDL oxidati
on was examined. We constructed the recombinant adenovirus AxCAEC-SOD expre
ssing human EC-SOD by CAG promoter. Infection of endothelial cells with AxC
AEC-SOD resulted in EC-SOD protein secretion in a dose-dependent manner and
a decrease of endothelial-cell-derived superoxide production. Moreover, it
was proven to coexist with heparan sulfate by immunohistochemical staining
. Endothelial-cell-mediated LDL oxidation enhanced by ferric-sodium EDTA wa
s inhibited by 47% in TEARS formation by AxCAEC-SOD infection, In agarose g
el electrophoresis, AxCAEC-SOD decreased the negative charge of oxidized LD
L by 50% and suppressed fragmentation of apolipoprotein B, These results su
ggested that human EC-SOD localized in the extracellular space and reduced
endothelial-cell-mediated LDL oxidation, In subendothelial space, EC-SOD bo
und on heparan sulfate might suppress LDL oxidation through reduction of su
peroxide anion, (C) 2001 Academic Press.