Oxidative stress plays a central role in
atherogenesis.
Antioxidants, such as
probucol, inhibit oxidation of
LDL, retard secretion of
interleukin-1,
growth factors and
chemoattractants, and thus inhibit progression of
atherosclerosis. Other
antioxidants with an ability to inhibit
LDL oxidation, however, could not prevent progression of
atherosclerosis. The inconsistency between
antioxidant potencies indicated oxidative events might have occurred at locations other than
LDL. MDA-
lysine epitope (
MDA-lys) is closely associated with
atherogenesis and was recognized as marker for oxidation. We traced formation of
MDA-lys during oxidation of
LDL and formation of foam cells. The results indicated that
thiobarbituric acid reactive substance (
TBARS) was primarily present in
lipid fraction of
ox-LDL not associated with
protein fraction after Cu2+ oxidation in vitro.
Oxidized LDL did not increase significant immunoreactivity of
MDA-lys epitope under our experimental conditions. Foam cells, however, showed the presence of
MDA-lys epitope suggesting that intracellular oxidation events occurred to internalized
lipids. The uptake of non-oxidatively modified
LDL (
acetylated LDL) was sufficient to generate
MDA-lys epitope in foam cells, consistent with the hypothesis that
atherosclerosis is associated with oxidative events in addition to
LDL oxidation. We hypothesized that
MDA-lys may be generated through intracellular lipid metabolism during the formation of foam cells.