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Determination of the lower threshold of apolipoprotein E resulting in remnant lipoprotein clearance1

Authors :
Alyssa H. Hasty
MacRae F. Linton
Larry L. Swift
Sergio Fazio
Source :
Journal of Lipid Research, Vol 40, Iss 8, Pp 1529-1538 (1999)
Publication Year :
1999
Publisher :
Elsevier, 1999.

Abstract

Apolipoprotein E (apoE) is the ligand for receptor-mediated clearance of remnant lipoproteins. ApoE at concentrations only 10% of normal, achieved through transplantation of wild-type marrow into apoE(–/–) mice, is sufficient for the maintenance of normal serum lipid and lipoprotein levels. The goal of the present study was to identify the minimal concentration of serum apoE still affecting cholesterol levels, and to determine whether any effects on remnant clearance below this level of apoE were detectable. ApoE(+/+) marrow was mixed with apoE(–/–) marrow in proportions of 1, 5, 10, and 25% to make chimeric mice with serum levels of apoE ranging from 0.005 to 0.46 mg/dl. Analysis of serum cholesterol and apoE levels demonstrated a positive correlation between apoE levels and cholesterol reduction (r = 0.83), with levels of 0.04 mg/dl representing the functional threshold level. There were no differences in lipoprotein profiles and clearance between apoE(–/–) mice and mice with serum apoE of less than 0.04 mg/dl, as assessed by FPLC, non-denaturing gel electrophoresis, and turnover studies. However, electron microscopy of negative stains showed fewer lipoprotein particles with a diameter of

Details

Language :
English
ISSN :
00222275
Volume :
40
Issue :
8
Database :
Directory of Open Access Journals
Journal :
Journal of Lipid Research
Publication Type :
Academic Journal
Accession number :
edsdoj.9f9c72aaa9fc46e19b915d91527f71c6
Document Type :
article
Full Text :
https://doi.org/10.1016/S0022-2275(20)33397-6