Renal injury in apolipoprotein E-deficient mice
Open accessAbstract
Hyperlipidemia is thought to accelerate the progression of renal diseases, but the mechanisms by which hyperlipidemia exerts its deleterious effect is still poorly understood. The aim of this study was to describe the renal pathology in a hyperlipidemic mouse strain, the apolipoprotein E-deficient mice (apoE-/-). Renal specimens from a total of 34 mice were studied, including 19 apoE-/- females at the age of 36 weeks, 9 apoE-/- females at the age of 24 weeks, and 6 wild-type females (C57BL/6) as controls. Kidneys were evaluated by histologic examination, immunohistochemistry, and electron microscopy. Immunohistochemistry was used to detect MAC-2-expressing monocyte/macrophages, and the proliferation marker PCNA. Glomerular cell number, glomerular matrix area, and glomerular area were quantified by morphometry. Glomerular lesions in apoE-/- mice were characterized by macrophage accumulation, commonly with foam cell appearance, deposition of extracellular matrix, glomerular hyperplasia, and at times prominent mesangiolysis associated with capillary microaneurysms. Some cases demonstrated lipid deposits filling glomerular capillaries. Arterioles of the vascular pole demonstrated a "foamy" degeneration of smooth muscle cells. These lesions related to hyperlipidemia in this well-established mouse strain have not been previously described. Because this mouse strain is among the most widely studied for interventions aimed at altering hyperlipidemia and the progression of atherosclerosis, we believe that our observations may be of major importance for the accurate interpretation of interventional studies in this strain and offer a new opportunity to study mechanisms of hyperlipidemic renal injury.
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apoE-/- and DKO mice have been reported to develop renal abnormalities that are different from those found in LPG.
“apoE Ϫ / Ϫ and DKO mice have been reported to develop renal abnormalities that are different from those found in LPG (40)(41)(42).”
From Macrophage-derived apoESendai suppresses atherosclerosis while causing lipoprotein glomerulopathy in hyperlipidemic mice (2014) · cites this paper as [41]
The Abstract reports renal injury in apoE-deficient mice and cites a study of renal injury in double-knockout mice. But the Discussion says that a lesion in the apoE-deficient mice resembles the lipoprotein thrombi of LPG, so this paper does not support a blanket claim that their renal abnormalities differ from those in LPG. (LLM, conf=0.88)
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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
ApoE-deficient mice develop lesions of all phases of atherosclerosis throughout the arterial tree.
Nakashima, Y., Plump, A. S., Raines, E. W., Breslow, J. L., & Ross, R. (1994) · Arteriosclerosis and Thrombosis: A Journal of Vascular Biology · doi:10.1161/01.atv.14.1.133 · Cited by 1,693 · see citing works
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CD36 and Na/K-ATPase-α1 Form a Proinflammatory Signaling Loop in Kidney
Kennedy, D. J., Chen, Y., Huang, W., Viterna, J., Liu, J., Westfall, K., Tian, J., Bartlett, D. J., Tang, W. H. W., Xie, Z., et al. (2013) · Hypertension · doi:10.1161/hypertensionaha.112.198770 · Cited by 101 · 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
Tsimihodimos, V., & Elisaf, M. (2011) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e328345ebb0 · Cited by 33 · 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
- Authors
- Wen, M., Segerer, S., Dantas, M., Brown, P. A., Hudkins, K. L., Goodpaster, T., Kirk, E., LeBoeuf, R. C., & Alpers, C. E.
- Affiliations
- University of Washington (US)
- University of Aberdeen (GB)
- Corresponding author
- Alpers, Charles E
- Venue
- Laboratory Investigation
- Publisher
- Elsevier BV
- Published
- 2002-08
- Volume
- 82
- Issue
- 8
- Pages
- 999-1006
- ISSN
- 0023-6837 (ISSN-L)
- OpenAlex
- W2113916200
- Cited by
- 104
- References
- 2
- Citations by year
- 2023: 3 · 2022: 4 · 2021: 4 · 2020: 2 · 2019: 4 · 2018: 1 · 2017: 5 · 2016: 6 · 2015: 7 · 2014: 9 · 2013: 6 · 2012: 8
- FWCI
- 2.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Laboratory Investigation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Else Kröner-Fresenius-Stiftung
- National Institutes of Health (DK47659)
- National Heart, Lung, and Blood Institute (HL52848, R01HL052848)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK47659, P50DK047659)
- Topics
- Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Renal and Vascular Pathologies
- Keywords
- ApoE-deficient mice, hyperlipidemia, kidney injury, glomerular lesions, macrophage accumulation, foam cells, extracellular matrix deposition, glomerular hyperplasia, mesangiolysis, lipid deposits, glomerular morphometry, galectin-3
- MeSH terms
- Animals, Antigens, Differentiation, Apolipoproteins E, Hyperlipidemias, Immunohistochemistry, Kidney, Kidney Glomerulus, Mice, Knockout, Galectin 3, Mice
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