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Titolo:
Determination of the lower threshold of apolipoprotein E resulting in remnant lipoprotein clearance
Autore:
Hasty, AH; Linton, MF; Swift, LL; Fazio, S;
Indirizzi:
Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 Dept Med, Nashville, TN 37232 USA Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 pt Pathol, Nashville, TN 37232 USA Vanderbilt Univ, Med Ctr, Dept Pharmacol, Nashville, TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 Pharmacol, Nashville, TN 37232 USA
Titolo Testata:
JOURNAL OF LIPID RESEARCH
fascicolo: 8, volume: 40, anno: 1999,
pagine: 1529 - 1538
SICI:
0022-2275(199908)40:8<1529:DOTLTO>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
BONE-MARROW TRANSPLANTATION; E-DEFICIENT MICE; DIET-INDUCED HYPERCHOLESTEROLEMIA; PLASMA-LIPOPROTEINS; TRANSGENIC MICE; III HYPERLIPOPROTEINEMIA; GENE REPLACEMENT; IN-VIVO; ATHEROSCLEROSIS; APOE;
Keywords:
apolipoprotein E; remnant lipoproteins; cholesterol; bone marrow transplantation;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Hasty, AH Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA Vanderbilt Univ Nashville TN USA 37232 Nashville, TN 37232 USA
Citazione:
A.H. Hasty et al., "Determination of the lower threshold of apolipoprotein E resulting in remnant lipoprotein clearance", J LIPID RES, 40(8), 1999, pp. 1529-1538

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 <30 nm in the serum of these mice compared to apoE(-/-) mice. These data demonstrate that the threshold of serum apoE resulting in cholesterol reduction is 0.04 mg/dl, and indicate that apoE below this level affects lipoprotein size distribution possibly by accelerating the clearance of smaller remnants.

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Documento generato il 04/12/20 alle ore 06:49:35