© 2001 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Glycoxidation and lipid peroxidation of low-density lipoprotein can synergistically enhance atherogenesis
aDepartment of Pathology, School of Medicine, Fukuoka University, Fukuoka 814-0180, Japan
bDepartment of Biochemistry, Kumamoto University School of Medicine, Kumamoto 860-0811, Japan
cDepartment of Pathology, Kumamoto University School of Medicine, Kumamoto 860-0811, Japan
dDepartment of Microbiology and Molecular Pathology, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 199-0195, Japan
eDepartment of Biochemistry, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita 565-0871, Osaka, Japan
* Corresponding author. Second Department of Pathology, School of Medicine, Fukuoka University, 45-1, 7-chome Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan. Tel.: +81-92-801-1011, ext. 3281; fax: +81-92-863-8383 nysakata{at}fukuoka-u.ac.jp
Objective: The purpose of this study was to clarify the role of glycoxidation and lipid peroxidation of low-density lipoprotein (LDL) in atherogenesis. Methods and results: We examined the formation of N
-(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.
KEYWORDS Atherosclerosis; Diabetes; Lipoproteins
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