Macrophages from nephrotic rats regulate apolipoprotein E biosynthesis and cholesterol content independently

Joseph Bass, Edward A. Fisher, Margaret M. Prack, David L. Williams, Julian B. Marsh*

*Corresponding author for this work

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

The effects of the nephrotic syndrome in rats on the cholesterol content and the biosynthesis of apolipoprotein E (apoE) by resident peritoneal macrophages have been investigated. Since the nephrotic syndrome has been associated with an increased risk of coronary atherosclerosis, we hypothesized that macrophages from nephrotic rats would accumulate cholesterol and undergo transformation into foam cells, with a concomitant increase in apoE biosynthesis. The nephrotic syndrome was induced in rats with puromycin aminonucleoside. Peritoneal macrophages exposed in vivo for 7-21 d to ascites fluid derived from plasma containing sixfold elevations of lipoproteins did not accumulate unesterified or esterified cholesterol. Nevertheless, immunoprecipitation assays after incubation of the isolated cells with [35S]methionine, or immunoblot analysis of the incubation medium demonstrated a 2.6-fold increase in apoE secretion compared with normal macrophages. This increase was accompanied by 5- to 10-fold increases in cellular apoE messenger RNA as determined by quantitative solution hybridization assay. Peritoneal macrophages cultured from nephrotic rats during the period of hypercholesterolemia also showed distinct and highly reproducible morphologic changes. The dissociation between apoE biosynthesis and macrophage cholesterol content provides new insight into the response of peritoneal macrophages in vivo to endogenous hyperlipemia.

Original languageEnglish (US)
Pages (from-to)470-475
Number of pages6
JournalJournal of Clinical Investigation
Volume87
Issue number2
DOIs
StatePublished - 1991

Keywords

  • Apoliproprotein E
  • Hypercholesterolemia
  • Macrophages
  • Nephrotic syndrome

ASJC Scopus subject areas

  • Medicine(all)

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