Glycolaldehyde-Modified Low Density Lipoprotein Leads Macrophages to Foam Cells via the Macrophage Scavenger Receptor
Abstract
It was shown that proteins modified with advanced glycation end products (AGE) are effectively endocytosed by macrophages or macrophage-derived cells in vitro, and immunohistochemical studies involving anti-AGE antibodies demonstrated the accumulation of AGE-modified proteins (AGE-proteins) in macrophage-derived foam cells in human atherosclerotic lesions in situ, suggesting the involvement of AGE-modified LDL in the atherogenic process in vivo. To examine this suggestion, LDL was modified with glycolaldehyde, a highly reactive intermediate of the Maillard reaction. Physicochemically, glycolaldehyde-modified LDL (GA-LDL) was characterized by increases in negative charge, fluorescence intensity, and reactivity to anti-AGE antibodies, properties highly similar to those of AGE-proteins. The cellular interaction of GA-LDL with mouse peritoneal macrophages showed that GA-LDL was specifically recognized and endocytosed, followed by lysosomal degradation. The endocytic uptake of GA-LDL by these cells was competitively inhibited by acetylated LDL (acetyl-LDL), and the endocytic degradation of acetyl-LDL was also competed for by GA-LDL. Furthermore, incubation of GA-LDL with these macrophages and Chinese hamster ovary cells overexpressing the macrophage scavenger receptor (MSR), but not with peritoneal macrophages from MSR-knockout mice, led to the intracellular accumulation of cholesteryl esters (CE). These results raised the possibility that AGE-modified LDL, if available in situ, is taken up by macrophages mainly via MSR and then contributes to foam cell formation in early atherosclerotic lesions.
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Glycated LDL cholesterol, once oxidized or AGE-modified, is recognized by scavenger receptors on macrophages and leads to the formation of foam cells.
“Glycated low density lipoprotein (LDL) cholesterol, once oxidized or AGE-modified, is recognized by scavenger receptors on macrophages and lead to the formation of foam cells.”
From The Vasculature in Prediabetes (2018) · cites this paper as [62]
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- Authors
- Jinnouchi, Y., Sano, H., Nagai, R., Hakamata, H., Kodama, T., Suzuki, H., Yoshida, M., Ueda, S., & Horiuchi, S.
- Affiliations
- Kumamoto University (JP)
- Research Center for Advanced Science and Technology, The University of Tokyo (JP)
- Chugai Pharmaceutical Co., Ltd. (Japan) (JP)
- Corresponding author
- Horiuchi, S.
- Venue
- Journal of Biochemistry
- Publisher
- Oxford University Press (OUP)
- Published
- 1998-06-01
- Volume
- 123
- Issue
- 6
- Pages
- 1208-1217
- ISSN
- 0021-924X (ISSN-L)
- OpenAlex
- W2034818821
- Cited by
- 48
- References
- 0
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 1 · 2016: 3 · 2013: 2 · 2012: 2
- FWCI
- 1.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- advanced glycation end products, macrophage scavenger receptor, foam cell formation, atherosclerosis, Maillard reaction, macrophage endocytosis, acetylated LDL, cholesteryl ester accumulation, lysosomal degradation, peritoneal macrophages
- MeSH terms
- Acetaldehyde, Animals, Cell Differentiation, Foam Cells, Glycosylation, Cricetinae, Humans, Lipoproteins, LDL, Macrophages, Membrane Proteins, Receptors, Immunologic, CHO Cells, Receptors, Lipoprotein, Mice, Knockout, Receptors, Scavenger, Scavenger Receptors, Class B, Mice
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