Abstract
We have shown that the dual domain peptide Ac-hE18A-NH2, in which LRKLRKRLLR, (141–150 region of human apo E) covalently linked to a class
A lipid-associating domain, is able to associate with apo B-containing lipoproteins
and enhance their clearance both in vitro and in vivo. We present here the differential
effects of this peptide on the plasma cholesterol levels in different mouse models.
The peptide intravenously administered (100 μg) into C57BL/6J mice on atherogenic
diet, apo E null, and apo E null/LDL-receptor (LDL-R) null double knock out mouse
models, was able to rapidly reduce plasma cholesterol levels within 2 min, and the
effect persisted for more than 6 h. The reduction was limited to the VLDL and IDL/LDL
fractions; HDL was not reduced in any mouse model studied. However, the peptide had
no effect on the plasma cholesterol levels in C57BL/6J mice on normal diet, LDL-R
null mice on normal chow, and LDL-R null mice on Western diet. Administration to LDL-R
null mice of 125I-labelled human lipoproteins incubated with peptide resulted in accelerated human
VLDL and LDL clearance with associated increase of radioactivity in the liver. These
results, coupled with our earlier in vitro observations, indicate that the Arg-rich
peptide-assisted rapid clearance of plasma cholesterol in dyslipidemic mice is due
to the peptide targeting apo B-48-containing atherogenic lipoproteins to the liver
for increased uptake and degradation.
Keywords
Abbreviations:
Apo, apolipoprotein (), VLDL, very low density lipoprotein (), IDL, intermediate density lipoprotein (), LDL, low density lipoprotein (), HDL, high density lipoprotein (), LDL-R, low density lipoprotein receptor (), Arg, arginine (), LRP, LDL-receptor-related protein (), LPL, lipoprotein lipase (), HSPG, heparan sulfate proteoglycan (), PBS, phosphate-buffered saline (), EDTA, ethylenediaminetetraacetic acid (), SDS, sodium dodecyl sulfate (), PAGE, polyacrylamide gel electrophoresis (), CLiP, column lipoprotein profiles ()To read this article in full you will need to make a payment
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Article info
Publication history
Accepted:
February 20,
2003
Received in revised form:
February 5,
2003
Received:
August 10,
2002
Identification
Copyright
© 2003 Elsevier Science Ireland Ltd. Published by Elsevier Inc. All rights reserved.
