Diminished LDL Receptor and High Heparin Binding of Apolipoprotein E2 Sendai Associated with Lipoprotein Glomerulopathy
Abstract
Abstract.: Variants of apolipoprotein E (apoE) have been linked to lipoprotein glomerulopathy, a new glomerular disease characterized by the deposition of lipoproteins in mesangial capillaries. One third of affected patients are heterozygous for apoE2 Sendai (Arg 145 Pro). Variants of apoE can also produce type III hyperlipoproteinemia (HLP). Recessive type III HLP is caused by apoE2 (Arg 158 Cys), a mutant with diminished low-density lipoprotein (LDL) receptor binding but halfnormal heparin binding. Dominant type III HLP is caused by mutations that markedly alter heparin binding but modestly reduce receptor binding. This study examined whether apoE2 Sendai (Arg 145 Pro) was functionally different from type III HLP-producing apoE variants by expressing apoE3, apoE2 (Arg 158 Cys), apoE1 (Arg 146 Glu), a dominant apoE variant, and apoE2 Sendai (Arg 145 Pro) in the baculovirus system. LDL receptor binding was studied using recombinant apoE complexed to phospholipid vesicles and to very lowdensity lipoprotein from a patient with familiar apoE deficiency. Compared with apoE3, receptor-binding activities of apoE2 (Arg 158 Cys), apoE1 (Arg 146 Glu), and apoE2 Sendai (Arg 145 Pro) all were less than 5%. Heparin-binding activities were 53%, 23%, and 66%, respectively, of apoE3. The distribution of apoE2 Sendai among the major plasma lipoprotein fractions was similar to that of apoE3 and apoE2 (Arg 158 Cys). ApoE2 Sendai (Arg 145 Pro) represents the only known mutation within the heparin-binding domain of apoE (residues 142 through 147), revealing diminished receptor binding and almost normal heparin binding. These unique characteristics of apoE2 Sendai (Arg 145 Pro) may relate to the development of lipoprotein glomerulopathy.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Some etiology studies using APOE Sendai suggest that reduced receptor-binding activity and thermodynamic abnormalities may play important roles in the pathogenesis of LPG.
“Some etiology studies using APOE Sendai suggest that the reduced receptor-binding activity [12] and thermodynamic abnormalities [13] may play important roles in the pathogenesis of LPG.”
From Lipoprotein glomerulopathy with a novel apolipoprotein E variant, APOE Kanto (Asp 151dup) (2024) · cites this paper as [12]
These mutations mitigate the binding ability of ApoE protein to LDL receptor, resulting in elevations of ApoE in the circulation, and could be an essential mechanism in LPG development.
“These mutations mitigate the binding ability of ApoE protein to LDL receptor, resulting in elevations of ApoE in the circulation, and could be an essential mechanism in the LPG development [12].”
From A case report of youth-onset lipoprotein glomerulopathy with APOE Chicago mutation (2024) · cites this paper as [12]
Many LPG-pathogenic APOE mutations are in or near the LDL receptor binding site, such as APOE Sendai (Arg145Pro), APOE Chicago (Arg147Pro), and APOE Las Vegas (Ala152Lys).
“Many LPG-pathogenic APOE gene mutations are in or near its binding site of LDL receptor, such as APOE Sendai (Arg145Pro), APOE Chicago (Arg147Pro) and APOE Las Vegas (Ala152Lys).”
From A case report of youth-onset lipoprotein glomerulopathy with APOE Chicago mutation (2024) · cites this paper as [12]
LPG-pathogenic APOE mutations interfere with hepatocyte uptake of mutated ApoE-containing lipoproteins, resulting in increased levels of ApoE in circulation.
“In summary, LPG-pathogenic APOE mutations interfere with hepatocyte uptake of mutated ApoE-containing lipoproteins, resulting in increased levels of ApoE in circulation.”
From A case report of youth-onset lipoprotein glomerulopathy with APOE Chicago mutation (2024) · cites this paper as [12]
The hyperlipidemia of LPG is usually attributed to reduced binding capacity of mutated apoE with the LDL receptor.
“The hyperlipidemia of LPG is usually attributed to reduced binding capacity of mutated apoE with the LDL receptor9, 16), just like type III HLP caused by APOE2 homozygosity.”
From The Novel Apolipoprotein E Mutation ApoE Chengdu (c.518T＞C, p.L173P) in a Chinese Patient with Lipoprotein Glomerulopathy (2018) · cites this paper as [9]
apoE Sendai is more effective than apoE2 in binding to HSPG.
“In addition, apoE Sendai is more effective than apoE2 in binding to HSPG ( 34 ).”
From Macrophage-derived apoESendai suppresses atherosclerosis while causing lipoprotein glomerulopathy in hyperlipidemic mice (2014) · cites this paper as [34]
Cites
Apolipoprotein E polymorphism and atherosclerosis.
Davignon, J., Gregg, R. E., & Sing, C. F. (1988) · Arteriosclerosis: An Official Journal of the American Heart Association, Inc. · doi:10.1161/01.atv.8.1.1 · Cited by 1,981 · see citing works
Rall, S. C., Weisgraber, K. H., Innerarity, T. L., & Mahley, R. W. (1982) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.79.15.4696 · Cited by 345 · see citing works
Lipoprotein Glomerulopathy: Glomerular Lipoprotein Thrombi in a Patient With Hyperlipoproteinemia
Saito, T., Sato, H., Kudo, K.-I., Oikawa, S.-I., Shibata, T., Hara, Y., Yoshinaga, K., & Sakaguchi, H. (1989) · American Journal of Kidney Diseases · doi:10.1016/s0272-6386(89)80134-9 · Cited by 148 · see citing works
Saito, T., Sato, H., Oikawa, S., Kudo, K., Kurihara, I., Nakayama, K., Abe, K., Yoshinaga, K., & Sakaguchi, H. (1993) · American Journal of Nephrology · doi:10.1159/000168591 · Cited by 57 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Apolipoprotein E–related glomerular disorders
Saito, T., Matsunaga, A., Fukunaga, M., Nagahama, K., Hara, S., & Muso, E. (2020) · Kidney International · doi:10.1016/j.kint.2019.10.031 · Cited by 77 · see citing works
Tsimihodimos, V., & Elisaf, M. (2011) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e328345ebb0 · Cited by 33 · see citing works
Wu, H., Yang, Y., & Hu, Z. (2018) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.41996 · Cited by 24 · see citing works
Mitani, A., Ishigami, M., Watase, K., Minakata, T., & Yamamura, T. (2011) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.7377 · Cited by 24 · see citing works
Fukunaga, M., Nagahama, K., Aoki, M., Shimizu, A., Hara, S., Matsunaga, A., Muso, E., & Saito, T. (2018) · Case Reports in Nephrology and Dialysis · doi:10.1159/000487919 · Cited by 14 · see citing works
Common Apolipoprotein E Gene Mutations Contribute to Lipoprotein Glomerulopathy in China
Han, J., Pan, Y., Chen, Y., Li, X., Xing, G., Shi, J., Hou, P., Zhang, H., & Wang, H. (2010) · Nephron Clinical Practice · doi:10.1159/000276578 · Cited by 13 · see citing works
Clinicopathological and genetic characteristics in Chinese patients with lipoprotein glomerulopathy
Zhang, B., Liu, Z.-H., Zeng, C.-H., Zheng, J.-M., Chen, H.-P., & Li, L.-S. (2008) · Journal of Nephrology · doi:10.1093/joneph/21.1.110 · Cited by 12 · see citing works
Tavori, H., Fan, D., Giunzioni, I., Zhu, L., Linton, M. F., Fogo, A. B., & Fazio, S. (2014) · Journal of Lipid Research · doi:10.1194/jlr.m049874 · Cited by 10 · see citing works
Lipoprotein glomerulopathy with a novel apolipoprotein E variant, APOE Kanto (Asp 151dup)
Yokochi, A., Matsunaga, A., Kanemoto, K., Tominaga, N., Uda, S., & Saito, T. (2024) · CEN Case Reports · doi:10.1007/s13730-024-00920-z · Cited by 3 · see citing works
A case report of youth-onset lipoprotein glomerulopathy with APOE Chicago mutation
Liu, Y., Cheng, Y., Wen, Y., Li, C., Chen, G., & Li, M. (2024) · BMC Nephrology · doi:10.1186/s12882-024-03515-z · Cited by 2 · see citing works
The First Case of Lipoprotein Glomerulopathy in a Patient With Male Infertility
Ye, C., Wang, Y., Liang, C., Wang, Y., Zhang, C., & Jiang, H. (2026) · Kidney Medicine · doi:10.1016/j.xkme.2026.101308
- Authors
- HOFFMANN, M. M., SCHARNAGL, H., PANAGIOTOU, E., BANGHARD, W. T., WIELAND, H., & MA[Combining Diaeresis]RZ, W.
- Affiliations
- University of Freiburg (DE)
- Venue
- Journal of the American Society of Nephrology
- Published
- 2001-03
- Volume
- 12
- Issue
- 3
- Pages
- 524-530
- ISSN
- 1046-6673 (ISSN-L)
- OpenAlex
- W2128153531
- Cited by
- 42
- References
- 4
- Citations by year
- 2026: 1 · 2024: 3 · 2022: 1 · 2019: 2 · 2018: 2 · 2017: 1 · 2016: 1 · 2015: 2 · 2014: 3 · 2013: 4 · 2012: 1
- FWCI
- 1.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of the American Society of Nephrology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- lipoprotein glomerulopathy, LDL receptor binding, heparin binding, type III hyperlipoproteinemia, APOE3, heparin-binding domain, apolipoprotein E deficiency
- MeSH terms
- Apolipoproteins E, Heparin, Heterozygote, Humans, Kidney Diseases, Protein Binding, Receptors, LDL, Recombinant Proteins, Genetic Variation, Mutagenesis, Site-Directed, Apolipoprotein E2, In Vitro Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
