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Cited by 53Cholesterol and Lipid MetabolismLipoproteins and Cardiovascular HealthAlzheimer's disease research and treatments

Isoform-Dependent Cholesterol Efflux From Macrophages by Apolipoprotein E Is Modulated by Cell Surface Proteoglycans

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Hara, Masumi, Matsushima, Teruhiko, Satoh, Hiroaki, Iso-o, Naoyuki, Noto, Hiroshi, Togo, Masako, Kimura, Satoshi, Hashimoto, Yoshiaki +1 more·2003·Arteriosclerosis, Thrombosis, and Vascular Biology
DOI 10.1161/01.atv.0000054199.78458.4b
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Abstract

Objective— Apolipoprotein E (apoE) mediates cellular cholesterol efflux and plays a crucial role in the inhibition of atherogenesis. We investigated whether there is an isoform-specific difference in its function for cholesterol efflux from cholesterol-loaded RAW264.7 cells, a murine macrophage cell line that lacks endogenous apoE expression. Methods and Results— When human apoE was expressed in RAW264.7 cells, apoE2 reduced cellular total cholesterol (TC) and esterified cholesterol (EC) levels significantly, whereas apoE3 and apoE4 had no effect. However, treatment of cells with 4-methylumbelliferyl-7-β- d -xyloside (β-DX) resulted in all 3 isoforms’ reducing cellular TC and EC contents significantly. We also investigated the effect of exogenously derived apoE on cholesterol efflux by utilizing the medium harvested from HeLa cells expressing apoE. ApoE2 and E3 reduced both cellular TC and EC contents significantly, whereas apoE4 did not. However, treatment of the cells with β-DX resulted in all 3 exogenously derived apoE isoforms’ reducing TC and EC contents significantly. The binding ability of apoE to heparan sulfate proteoglycans examined by heparinase I treatment revealed less binding ability of apoE2 compared with that of apoE3 or apoE4. Conclusions— The present study clarified the differential cellular cholesterol-modulating effect of apoE isoforms in macrophages, which would be due to the difference in their binding to proteoglycans.

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Authors
Hara, M., Matsushima, T., Satoh, H., Iso-o, N., Noto, H., Togo, M., Kimura, S., Hashimoto, Y., & Tsukamoto, K.
Affiliations
Tsukuba Memorial Hospital (JP)
ORCID
Venue
Arteriosclerosis, Thrombosis, and Vascular Biology
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2003-02
Volume
23
Issue
2
Pages
269-274
ISSN
  • 1079-5642 (ISSN-L)
  • 1524-4636
DOI
10.1161/01.atv.0000054199.78458.4b
OpenAlex
W2166878600
Cited by
53
References
37
Citations by year
2025: 3 · 2024: 2 · 2023: 3 · 2021: 2 · 2020: 3 · 2019: 3 · 2018: 2 · 2016: 2 · 2014: 5 · 2013: 3 · 2012: 3
FWCI
1.35
Type
journal article
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by-nc-nd)
Topics
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
apolipoprotein E, APOE isoforms, APOE2, APOE3, APOE ε4, cholesterol efflux, macrophages, heparan sulfate proteoglycans, esterified cholesterol, atherogenesis, RAW 264.7 macrophages
MeSH terms
Adenoviridae, Animals, Antigens, Surface, Apolipoproteins E, beta-Galactosidase, Cell Line, Cholesterol, Genetic Vectors, HeLa Cells, Humans, Lipoproteins, VLDL, Proteoglycans, Transfection, Tumor Cells, Cultured, Macrophages, Peritoneal, Gene Transfer Techniques, Heparin Lyase, Mice, Apolipoprotein E3, Apolipoprotein E4

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