Interaction of endothelial cells and triglyceride-rich lipoproteins with apolipoprotein E (Arg25[rarr ]Cys) from a patient with lipoprotein glomerulopathy
Abstract
We saw a patient with proteinuria and characteristics of lipoprotein glomerulopathy (LPG). Histologic analysis of renal biopsy showed a thrombus-like substance in the markedly dilated glomerular capillaries, which stained positive with oil red O. Increased concentration of plasma apolipoprotein E (apoE) was also noted. Those findings are consistent with the diagnostic criteria of LPG, as reported by Oikawa et al. In isoelectric focusing gel electrophoresis of apoE, a band (apoE3') between apoE3 and E2 was observed. The patient's DNA sequence exhibited a C to G substitution in exon 3 of the apoE gene at the position of the 25th amino acid, resulting in an amino acid substitution of the arginine residue for cysteine residue. To clarify the pathophysiologic role of this mutation, we investigated the binding and the uptake of apoE3' triglyceride-rich lipoproteins to human umbilical vein endothelial cells (HUVEC). The binding of apoE3'-triglyceride-rich lipoproteins to the cell-surface of HUVEC increased up to 30% to 50%, compared with apoE3-triglyceride-rich lipoproteins. But the uptake of apoE3'-triglyceride-rich lipoproteins into the cells was not different between them. These findings are consistent with the idea that an increase in binding of triglyceride-rich lipoproteins possessing apoE (Arg(25)-->Cys) to endothelial cells may promote deposition of lipid in the glomerular capillaries.
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Triglyceride-rich lipoprotein containing ApoE Kyoto has increased affinity for endothelial cells, which may manifest as local adhesion.
“triglyceride-rich lipoprotein containing ApoE Kyoto had been shown to have increased affinity for endothelial cells, and this may be manifested as local adhesion [14].”
From Lipoprotein glomerulopathy induced by ApoE Kyoto mutation in ApoE-deficient mice (2021) · cites this paper as [14]
Mutated ApoE-containing lipoproteins have higher aggregation tendency and are prone to interact with glomerular capillary endothelial cells and deposit in the glomerulus, which together lead to LPG pathogenesis.
“These mutated lipoproteins are with higher aggregation tendency and prone to interact with glomerular capillary endothelial cells and deposit in the glomerulus, which together lead to the pathogenesis of LPG.”
From A case report of youth-onset lipoprotein glomerulopathy with APOE Chicago mutation (2024) · cites this paper as [19]
Mutated ApoE exhibits increased affinity to endothelial cells, as found in APOE Kyoto (Arg25Cys) and APOE Chicago (Arg147Pro), which helps drive lipoproteins to deposit primarily in the capillary lumina of glomerulus and eventually cause LPG.
“Moreover, mutated ApoE also exhibits increased affinity to endothelial cells, as found in APOE Kyoto (Arg25Cys) and APOE Chicago (Arg147Pro), which help drive lipoproteins to deposit primarily in the capillary lumina of glomerulus and eventually cause LPG [7, 19].”
From A case report of youth-onset lipoprotein glomerulopathy with APOE Chicago mutation (2024) · cites this paper as [19]
Mutated apoE exhibits enhanced binding to glomerular capillaries, which might be a part of the pathogenic mechanism of LPG.
“These studies suggest that mutated apoE exhibits enhanced binding to glomerular capillaries, which might be a part of the pathogenic mechanism of LPG.”
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 [20]
The glomerular subendothelium is an ideal nesting spot for LPG-mutated lipoprotein to accumulate because mutated apoE has a higher affinity to both endothelial cells and the glomerular basement membrane.
“The glomerular subendothelium is an ideal nesting spot for LPG-mutated lipoprotein to accumulate since mutated apoE has a higher affinity to both endothelial cells and the glomerular basement membrane.”
From Lipoprotein Glomerulopathy, First Case Report from Canada (2022) · cites this paper as [43]
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- Authors
- Murano, T., Matsumura, R., Misawa, Y., Ozaki, H., Miyashita, Y., Yoshida, S., Sueioshi, M., Sugiyama, T., & Shirai, K.
- Affiliations
- Toho University (JP)
- Venue
- Metabolism
- Publisher
- Elsevier BV
- Published
- 2002-02
- Volume
- 51
- Issue
- 2
- Pages
- 201-205
- ISSN
- 0026-0495 (ISSN-L)
- OpenAlex
- W2031982429
- Cited by
- 27
- References
- 0
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2022: 2 · 2021: 3 · 2019: 1 · 2018: 2 · 2016: 1 · 2013: 2
- FWCI
- 0.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Metabolism (publishedVersion)
- 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, triglyceride-rich lipoproteins, endothelial cell adhesion, lipoprotein uptake, human umbilical vein endothelial cells, proteinuria
- MeSH terms
- Adult, Apolipoproteins E, Arginine, Cysteine, Endothelium, Humans, Isoelectric Focusing, Kidney Diseases, Kidney Glomerulus, Lipoproteins, Male, Triglycerides, Amino Acid Substitution
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