We examined the formation of
N(epsilon)-(carboxymethyl) lysine (CML), a glycoxidation product, and
malondialdehyde (MDA), a lipid peroxidation product, in vitro and their co-localization in human atherosclerotic lesions. Immunochemical analysis revealed that CML was formed in a time-dependent manner by human
LDL incubated with
copper ions and
glucose, i.e. an in vitro model of glycoxidation of
LDL. When
LDL was exposed to
copper ions alone, a small amount of CML was formed, however this was significantly less in
oxidized LDL than glycoxidative
LDL. In contrast, MDA formation was observed in both oxidation and glycoxidation of
LDL, but not in glycation of
LDL.
Hexitol-
lysine (HL), an Amadori product, was formed by both glycation and glycoxidation of
LDL, but not by oxidation of
LDL. Immunohistochemical analysis showed that CML and MDA accumulated mainly in macrophage/foam cells, while
pyrraline, a non-oxidative product of glycation, and
apolipoprotein B were localized in the extracellular matrix in atherosclerotic lesions.
Atheromas were positive for CML and MDA, but negative for
pyrraline. Macrophage/foam cells in atherosclerotic lesions exhibited co-localization of
macrophage scavenger receptor-A with CML and MDA, but not with
pyrraline.
CONCLUSION: