Virus-mediated Transduction of Apolipoprotein E (ApoE)-Sendai Develops Lipoprotein Glomerulopathy in ApoE-deficient Mice
Open accessAbstract
Lipoprotein glomerulopathy (LPG) is a unique renal disease characterized by thrombus-like substances in markedly dilated glomerular capillaries, dysbetalipoproteinemia, and elevated plasma concentrations of apoE. Recent studies identified several apoE mutations in patients with LPG, including apoE2(R145P) Sendai (apoE-Sendai). Virus-mediated transduction of apoE-Sendai in apoE-deficient hypercholesterolemic mice resulted in insufficient correction of hypercholesterolemia and a marked and temporal induction of plasma triglyceride levels. In vitro binding studies showed that apoE-Sendai has a reduced affinity for the low density lipoprotein receptor, suggesting that dysbetalipoproteinemia in LPG is caused by the apoE mutation. Furthermore, histological examination revealed marked intraglomerular depositions of apoE-containing lipoproteins in mice injected with apoE-Sendai virus. These LPG-like depositions were detected 6 days after virus injection and were sustained for at least 60 days. Our results demonstrated that apoE-Sendai is an etiological cause of LPG.
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ApoE Sendai is located in the LDLR binding area, and its affinity for LDLR is decreased.
“ApoE Sendai is located in the LDLR binding area, and the affinity of ApoE Sendai for LDLR was decreased [10].”
From Lipoprotein glomerulopathy induced by ApoE Kyoto mutation in ApoE-deficient mice (2021) · cites this paper as [10]
In the study by Yamamoto, expression of ApoE Sendai resulted in insufficient normalization of hypercholesterolemia in ApoE-deficient mice and induced high plasma levels of triglyceride.
“In the study by Yamamoto, the expression of ApoE Sendai resulted in insufficient normalization of hypercholesterolemia in ApoE-deficient mice and induced high plasma levels of triglyceride [10].”
From Lipoprotein glomerulopathy induced by ApoE Kyoto mutation in ApoE-deficient mice (2021) · cites this paper as [10]
Yamamoto et al. proved the pathogenicity of ApoE Sendai by developing LPG in ApoE-deficient mice using virus-mediated transduction of ApoE Sendai.
“Yamamoto et al. proved the pathogenicity of ApoE Sendai by developing LPG in ApoE-deficient mice using virus-mediated transduction of ApoE Sendai [10].”
From Lipoprotein glomerulopathy induced by ApoE Kyoto mutation in ApoE-deficient mice (2021) · cites this paper as [10]
Animal studies show that virus-mediated transduction of apoE2 in apoE−/− mice does not promote LPG-like intraglomerular depositions, in contrast to LPG-like depositions following apoE Sendai virus injection.
“This is supported further by animal studies showing that virus-mediated transduction of apoE2 in apoE / mice does not promote LPG-like intraglomerular depositions, in contrast to the presence of LPG-like depositions following apoE Sendai virus injection (26).”
From Thermodynamic destabilization and aggregation propensity as the mechanism behind the association of apoE3 mutants and lipoprotein glomerulopathy (2018) · cites this paper as [26]
ApoE dysfunction may be an etiological cause of LPG.
“These findings suggested that apoE dysfunction may be an etiological cause of LPG, although the exact mechanism remains elusive.”
From Thermodynamic destabilization and aggregation propensity as the mechanism behind the association of apoE3 mutants and lipoprotein glomerulopathy (2018) · cites this paper as [26]
The direct relation of apoE mutations with LPG is supported by gene transfer studies of apoE Sendai (R145P) to apoE-deficient mice that lead to lipoprotein depositions in the glomerulus of the kidney.
“The direct relation of apoE mutations with LPG has been supported by gene transfer studies of apoE Sendai (R145P), the second more frequent apoE mutant detected in LPG patients, to apoE-deficient mice that lead to lipoprotein depositions in the glomerulus of the kidney (26).”
From Thermodynamic destabilization and aggregation propensity as the mechanism behind the association of apoE3 mutants and lipoprotein glomerulopathy (2018) · cites this paper as [26]
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 [16]
In animal models, APOE Sendai (Arg145Pro) and APOE Kyoto (Arg25Cys) variants have been expressed in APOE-deficient mice, with LPG-like renal pathology having been observed in each.
“In animal models, APOE Sendai (Arg145Pro) and APOE Kyoto (Arg25Cys) variants have been expressed in APOE-deficient mice, with LPG-like renal pathology having been observed in each95, 96).”
From Impact of Apolipoprotein E Variants: A Review of Naturally Occurring Variants and Clinical Features (2025) · cites this paper as [95]
Although the apoE Sendai mutation has been directly linked to LPG, the pathogenesis of the disease is not defined.
“Although the apoE Sendai mutation has been directly linked to LPG (30)(31)(32)(33), the pathogenesis of the disease is not defi ned.”
From Macrophage-derived apoESendai suppresses atherosclerosis while causing lipoprotein glomerulopathy in hyperlipidemic mice (2014) · cites this paper as [30]
The pathogenetic role of apoE Sendai in LPG has been proven with the replication of an experimental LPG phenotype in mice after adenovirus-driven expression of apoE Sendai.
“The pathogenetic role of apoE Sendai in LPG has been proven with the replication of an experimental LPG phenotype in mice after adenovirus-driven expression of apoE Sendai ( 30 ).”
From Macrophage-derived apoESendai suppresses atherosclerosis while causing lipoprotein glomerulopathy in hyperlipidemic mice (2014) · cites this paper as [30]
Although its mutation is in the receptor binding domain, apoE Sendai is capable of efficient lipoprotein clearance, and its expression decreases serum cholesterol levels in apoE-/- mice.
“Although its mutation is in the receptor binding domain, apoE Sendai is capable of effi cient lipoprotein clearance, and its expression decreases serum cholesterol levels in apoE Ϫ / Ϫ mice ( 30 ).”
From Macrophage-derived apoESendai suppresses atherosclerosis while causing lipoprotein glomerulopathy in hyperlipidemic mice (2014) · cites this paper as [30]
apoE Sendai has functional characteristics distinct from other apoE mutants, such as increased binding to HSPGs and reduced binding to the LDLR.
“apoE Sendai has functional characteristics distinct from other apoE mutants, such as increased binding to HSPGs and reduced binding to the LDLR ( 30 ).”
From Macrophage-derived apoESendai suppresses atherosclerosis while causing lipoprotein glomerulopathy in hyperlipidemic mice (2014) · cites this paper as [30]
Cites
A Receptor-Mediated Pathway for Cholesterol Homeostasis
Brown, M. S., & Goldstein, J. L. (1986) · Science · doi:10.1126/science.3513311 · Cited by 5,703 · see citing works
Apolipoprotein E: Cholesterol Transport Protein with Expanding Role in Cell Biology
Mahley, R. W. (1988) · Science · doi:10.1126/science.3283935 · Cited by 4,028 · see citing works
Plump, A. S., Smith, J. D., Hayek, T., Aalto-Setälä, K., Walsh, A., Verstuyft, J. G., Rubin, E. M., & Breslow, J. L. (1992) · Cell · doi:10.1016/0092-8674(92)90362-g · Cited by 2,263 · see citing works
Spontaneous Hypercholesterolemia and Arterial Lesions in Mice Lacking Apolipoprotein E
Zhang, S. H., Reddick, R. L., Piedrahita, J. A., & Maeda, N. (1992) · Science · doi:10.1126/science.1411543 · Cited by 2,237 · see citing works
The Response-to-Retention Hypothesis of Early Atherogenesis
Williams, K. J., & Tabas, I. (1995) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.15.5.551 · Cited by 1,413 · see citing works
Takahashi, S., Kawarabayasi, Y., Nakai, T., Sakai, J., & Yamamoto, T. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.19.9252 · Cited by 550 · see citing works
Self-citationHandbook of Lipoprotein Testing
Rifai, N., Warnick, G. R., & Dominiczak, M. H. (2001) · Medical Entomology and Zoology · Cited by 361 · see citing works
Sterol Regulation of Fatty Acid Synthase Promoter
Bennett, M. K., López, J. M., Sanchez, H. B., & Osborne, T. F. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.43.25578 · Cited by 336 · see citing works
Borén, J., Olin, K., Lee, I., Chait, A., Wight, T. N., & Innerarity, T. L. (1998) · Journal of Clinical Investigation · doi:10.1172/jci2265 · Cited by 320 · see citing works
Handbook of lipoprotein testing
Contois, J. H. (2001) · Clinica Chimica Acta · doi:10.1016/s0009-8981(01)00486-7 · Cited by 224 · 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
Self-citationKashyap, V. S., Santamarina-Fojo, S., Brown, D. R., Parrott, C. L., Applebaum-Bowden, D. M., Meyn, S. M., Talley, G. D., Paigen, B. J., Maeda, N., & Brewer, H. B. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118200 · Cited by 148 · see citing works
Oikawa, S., Matsunaga, A., Saito, T., Sato, H., Seki, T., Hoshi, K., Hayasaka, K., Kotake, H., Midorikawa, H., Sekikawa, A., et al. (1997) · Journal of the American Society of Nephrology · doi:10.1681/asn.v85820 · Cited by 103 · see citing works
Self-citationTsukamoto, K., Smith, P., Glick, J. M., & Rader, D. J. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119501 · Cited by 92 · see citing works
A novel apolipoprotein E mutation, E2 (Arg25Cys), in lipoprotein glomerulopathy
Matsunaga, A., Sasaki, J., Komatsu, T., Kanatsu, K., Tsuji, E., Moriyama, K., Koga, T., Arakawa, K., Oikawa, S., Saito, T., et al. (1999) · Kidney International · doi:10.1046/j.1523-1755.1999.00572.x · Cited by 91 · see citing works
Self-citationMahley, R. W. (1991) · JAMA · doi:10.1001/jama.265.1.78 · Cited by 71 · see citing works
Abnormal Lipoprotein and Apolipoprotein Pattern in Lipoprotein Glomerulopathy
Oikawa, S., Suzuki, N., Sakuma, E., Saito, T., Namai, K., Kotake, H., Fujii, Y., & Toyota, T. (1991) · American Journal of Kidney Diseases · doi:10.1016/s0272-6386(12)80649-4 · Cited by 60 · see citing works
Self-citationUsui, S., Nakamura, M., Jitsukata, K., Nara, M., Hosaki, S., & Okazaki, M. (2000) · Clinical Chemistry · doi:10.1093/clinchem/46.1.63 · Cited by 57 · see citing works
Self-citationKonishi, K., Saruta, T., Kuramochi, S., Oikawa, S., Saito, T., Han, H., Matsunaga, A., & Sasaki, J. (1999) · Nephron · doi:10.1159/000045513 · Cited by 54 · see citing works
Self-citationA novel 18-amino acid deletion in apolipoprotein E associated with lipoprotein glomerulopathy
Ando, M., Sasaki, J., Hua, H., Matsunaga, A., Uchida, K., Jou, K., Oikawa, S., Saito, T., & Nihei, H. (1999) · Kidney International · doi:10.1046/j.1523-1755.1999.00677.x · Cited by 53 · see citing works
Self-citationLipoprotein glomerulopathy: renal lipidosis induced by novel apolipoprotein E variants
Saito, T., Oikawa, S., Sato, H., & Sasaki, J. (1999) · Nephron · doi:10.1159/000045511 · Cited by 46 · see citing works
Self-citationGenetic Defects in Lipoprotein Metabolism
Mahley, R. W. (1991) · JAMA · doi:10.1001/jama.1991.03460010078035 · Cited by 46 · see citing works
A new variant of apolipoprotein E (apo E Maebashi) in lipoprotein glomerulopathy
Ogawa, T., Maruyama, K., Hattori, H., Arai, H., Kondoh, I., Egashira, T., Watanabe, T., Kobayashi, Y., & Morikawa, A. (2000) · Pediatric Nephrology · doi:10.1007/s004670050032 · Cited by 37 · see citing works
Okazaki, M., Komoriya, N., Tomoike, H., Inoue, N., Usui, S., Itoh, S., & Hosaki, S. (1998) · Journal of Chromatography B Biomedical Sciences and Applications · doi:10.1016/s0378-4347(98)00064-4 · Cited by 30 · see citing works
Self-citationShibui, T., Uchida-Kamizono, M., Okazaki, H., Kondo, J., Murayama, S., Morimoto, Y., Nagahari, K., & Teranishi, Y. (1991) · Journal of Biotechnology · doi:10.1016/0168-1656(91)90002-d · Cited by 12 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Reversal of ApoE4-induced recycling block as a novel prevention approach for Alzheimer’s disease
Xian, X., Pohlkamp, T., Durakoglugil, M. S., Wong, C. H., Beck, J. K., Lane-Donovan, C., Plattner, F., & Herz, J. (2018) · eLife · doi:10.7554/elife.40048 · Cited by 98 · see citing works
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
Self-citationArai, T., Yamashita, S., Yamane, M., Manabe, N., Matsuzaki, T., Kiriyama, K., Kanayama, Y., Himeno, S., & Matsuzawa, Y. (2003) · Atherosclerosis · doi:10.1016/s0021-9150(03)00194-1 · Cited by 43 · see citing works
Georgiadou, D., Stamatakis, K., Efthimiadou, E. K., Kordas, G., Gantz, D., Chroni, A., & Stratikos, E. (2013) · Journal of Lipid Research · doi:10.1194/jlr.m030965 · Cited by 37 · 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
Katsarou, M., Stratikos, E., & Chroni, A. (2018) · Journal of Lipid Research · doi:10.1194/jlr.m088732 · Cited by 22 · see citing works
Impact of Apolipoprotein E Variants: A Review of Naturally Occurring Variants and Clinical Features
Matsunaga, A., & Saito, T. (2025) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.65393 · Cited by 14 · see citing works
Self-citationCommon 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
Lipoprotein glomerulopathy induced by ApoE Kyoto mutation in ApoE-deficient mice
Wu, H., Yang, J., Liu, Y.-Q., Lei, S., Yang, M., Yang, Z., Yang, Y., & Hu, Z. (2021) · Journal of Translational Medicine · doi:10.1186/s12967-021-02765-x · Cited by 10 · 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
- Authors
- Ishigaki, Y., Oikawa, S., Suzuki, T., Usui, S., Magoori, K., Kim, D.-H., Suzuki, H., Sasaki, J., Sasano, H., Okazaki, M., Toyota, T., Saito, T., & Yamamoto, T. T.
- Affiliations
- Tohoku University (JP)
- Tokyo Medical and Dental University (JP)
- Fukuoka University (JP)
- Corresponding author
- Yamamoto, Tokuo T.
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2000-10
- Volume
- 275
- Issue
- 40
- Pages
- 31269-31273
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2159091343
- Semantic Scholar
- 293da55b9faa108cf24004cdaaf632d8d48e3d9d
- Cited by
- 58
- References
- 25
- Citations by year
- 2026: 1 · 2025: 2 · 2022: 1 · 2021: 4 · 2019: 1 · 2018: 3 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 5 · 2013: 2 · 2012: 2
- FWCI
- 2.23
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- lipoprotein glomerulopathy, apolipoprotein E, ApoE-deficient mice, dysbetalipoproteinemia, hypercholesterolemia, plasma triglycerides
- MeSH terms
- Adenoviridae, Animals, Apolipoproteins E, Chromatography, High Pressure Liquid, Hypercholesterolemia, Kidney Diseases, Kinetics, Male, Mice, Mutant Strains, Protein Binding, Receptors, LDL, Time Factors, Transduction, Genetic, Triglycerides, Gene Transfer Techniques, Respirovirus, Mice
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