Virus-mediated transduction of apolipoprotein E (ApoE)-Sendai develops lipoprotein glomerulopathy in ApoE-deficient mice

Yasushi Ishigaki, Shinichi Oikawa, Takashi Suzuki, Shinichi Usui, Kenta Magoori, Dong Ho Kim, Hiroyuki Suzuki, Jun Sasaki, Hironobu Sasano, Mitsuyo Okazaki, Takayoshi Toyota, Takao Saito, Tokuo T. Yamamoto

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54 Citations (Scopus)

Abstract

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) Sendal (apoE-Sendai). Virus-mediated transduction of apoE-Sendai in apoE-deficient hypereholesterolemic mice resulted in insufficient correction of hypercholesterolemia and a marked and temporal induction of plasma triglyceride levels. In vitro binding studies showed that apoE-Sendal 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 69 days. Our results demonstrated that apoE-Sendai is an etiological cause of LPG.

Original languageEnglish
Pages (from-to)31269-31273
Number of pages5
JournalJournal of Biological Chemistry
Volume275
Issue number40
DOIs
Publication statusPublished - Oct 6 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    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. (2000). Virus-mediated transduction of apolipoprotein E (ApoE)-Sendai develops lipoprotein glomerulopathy in ApoE-deficient mice. Journal of Biological Chemistry, 275(40), 31269-31273. https://doi.org/10.1074/jbc.M005906200