Increased atherosclerotic lesions in apoE mice with plasma phospholipid transfer protein overexpression.
OBJECTIVE
Plasma phospholipid transfer protein (PLTP) is involved in the metabolism of HDL and apolipoprotein B (apoB)-containing lipoproteins. Atherosclerosis susceptibility is decreased in mice with PLTP deficiency that is associated with decreased liver production of apoB-containing lipoproteins and increase in their antioxidant. To investigate additionally the effect of PLTP on the development of atherosclerosis, we overexpressed PLTP in mice.


RESULTS
PLTP was overexpressed in apoE knockout mice using an adenovirus-associated virus (AAV)-mediated system. Plasma PLTP activity was 1.3- to 2-fold higher in mice injected with AAV-PLTP than in mice injected with control AAV-GFP, and PLTP levels were sustained during the experiment period (4 months). We show that 2-fold increased PLTP activity results in (1) a decrease in HDL cholesterol, HDL phospholipid, and apoAI levels; (2) a decrease in vitamin E contents in total plasma and in individual lipoprotein fractions; (3) an increase in lipoprotein oxidizability as assessed by copper-induced formation of conjugated dienes; (4) an increase in autoantibodies against oxidized apoB-containing particles; and (5) an increase in atherosclerosis lesions in proximal aorta.


CONCLUSIONS
These observations indicate that elevated plasma PLTP levels constitute a novel, long-term risk factor for atherosclerosis.
Yang
Xiao Ping
XP
Department of Anatomy and Cell Biology, State University of New York, Downstate Medical Center, Brooklyn, NY 11203, USA.
Yan
Daoguang
D
Qiao
Chunping
C
Liu
Rui Jie
RJ
Chen
Jer-Gin
JG
Li
Juan
J
Schneider
Martina
M
Lagrost
Laurent
L
Xiao
Xiao
X
Jiang
Xian-Cheng
XC
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D001161:Arteriosclerosis / Q000097:blood / Q000209:etiology*; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000097:blood* / Q000235:genetics; D005260:Female; D005822:Genetic Vectors; D007267:Injections; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000097:blood* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D010084:Oxidation-Reduction / Q000187:drug effects; D049294:Phospholipid Transfer Proteins; D024502:alpha-Tocopherol / Q000378:metabolism
D001057:Apolipoproteins E; D002352:Carrier Proteins; D008055:Lipids; D008074:Lipoproteins; D008565:Membrane Proteins; D049294:Phospholipid Transfer Proteins; D024502:alpha-Tocopherol