Glycoxidation and lipid peroxidation of low-density lipoprotein can synergistically enhance atherogenesis.
Cardiovasc Res
; 49(2): 466-75, 2001 Feb 01.
Article
en En
| MEDLINE
| ID: mdl-11164857
ABSTRACT
OBJECTIVE:
The purpose of this study was to clarify the role of glycoxidation and lipid peroxidation of low-density lipoprotein (LDL) in atherogenesis. METHODS ANDRESULTS:
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:
Our results suggest that glycoxidation and lipid peroxidation of LDL synergistically promote the development of atherosclerotic lesions through interaction with macrophage scavenger receptor-A.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Arteriosclerosis
/
Lipoproteínas LDL
/
Lisina
/
Malondialdehído
Límite:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Cardiovasc Res
Año:
2001
Tipo del documento:
Article
País de afiliación:
Japón