Title
Adenovirus mediated overexpression of human phospholipid transfer protein alters plasma HDL levels in mice
Author
Gaubius Instituut TNO
Ehnholm, S.
van Dijk, K.W.
van Hof, B.
van Zee, A.D.
Olkkonen, V.M.
Jauhiainen, M.
Hofker, M.
Havekes, L.
Ehnholm, C.
Publication year
1998
Abstract
To study the function of plasma phospholipid transfer protein (PLTP) in vivo, a liver directed adenoviral gene transfer system was used to overexpress human PLTP in mice. For the experiments, two strains of mice, wild type (C57/B1) and mice transgenic for the human apoA-I gene (HuApoA- ITg), were utilized. Five days after injection of the recombinant PLTP adenovirus, wild type mice showed a 4-fold increase in serum PLTP activity in (12.2 ± 1.3 umol/ml/per h to 48.1 ± 8.6 umol/ml per h (+394%), P < 0.001). The PLTP overexpression induced significant reduction of serum cholesterol (2.46 ± 0.08 to 0.69 ± 0.42 mmol/l (-72%), P < 0.001), phospholipids (3.10 ± 0.06 to 0.90 ± 0.24 mmol/l (-71%), P < 0.01), and triglycerides (0.2 ± 0.07 to 0.08 ± 0.03 mmol/l (-69%), (P < 0.001). ApoA- I was hardly detectable in the serum. These lipid changes were due to a dramatic reduction of high density lipoprotein (HDL). The HuApoA-ITg mice displayed higher basal HDL level and PLTP activity. Adenovirus mediated PLTP overexpression in these mice resulted in a similar decrease of the lipid levels as that seen in the C57/Bl mice. However, the lipoprotein profile revealed a redistribution of HDL, with the appearance of larger buoyant HDL species. The results demonstrate that plasma phospholipid transfer protein in vivo causes high density lipoprotein (HDL) conversion and thereby plays a central role in HDL metabolism.
Subject
Apolipoprotein A-I
HDL conversion
HDL metabolism
Lipid metabolism
Phospholipid transfer protein
Recombinant adenovirus
Adenoviridae
Animals
Apolipoprotein A-I
Carrier Proteins
Cholesterol
Cholesterol Esters
Female
Genetic Vectors
Humans
Lipoproteins
Lipoproteins, HDL
Liver
Membrane Proteins
Mice
Mice, Inbred C57BL
Mice, Transgenic
Phospholipid Transfer Proteins
Phospholipids
Recombinant Proteins
Triglycerides
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TNO identifier
234473
ISSN
0022-2275
Source
Journal of Lipid Research, 39 (39), 1248-1253
Document type
article