Elevation of plasma phospholipid transfer protein in transgenic mice increases VLDL secretion
2002
textabstractTwo lipid transfer proteins are active in human plasma, cholesteryl ester
transfer protein (CETP), and phospholipid transfer protein (PLTP). Mice by
nature do not express CETP. Additional inactivation of the PLTP gene
resulted in reduced secretion of VLDL and subsequently in decreased
susceptibility to diet-induced atherosclerosis. The aim of this study is
to assess possible effects of differences in PLTP expression on VLDL
secretion in mice that are proficient in CETP and PLTP. We compared human
CETP transgenic (huCETPtg) mice with mice expressing both human lipid
transfer proteins (huCETPtg/huPLTPtg). Plasma cholesterol in huCETPtg mice
was 1.5-fold higher compared with huCETPtg/huPLTPtg mice (P < 0.001). This
difference was mostly due to a lower HDL level in the huCETPtg/huPLTPtg
mice, which subsequently could lead to the somewhat decreased CETP
activity and concentration that was found in huCETPtg/huPLTPtg mice (P <
0.05). PLTP activity was 2.8-fold increased in these animals (P < 0.001).
The human PLTP concentration was 5 microg/ml. Moderate overexpression of
PLTP resulted in a 1.5-fold higher VLDL secretion compared with huCETPtg
mice (P < 0.05). The composition of nascent VLDL was similar in both
strains. These results indicate that elevated PLTP activity in huCETPtg
mice results in an increase in VLDL secretion. In addition, PLTP
overexpression decreases plasma HDL cholesterol as well as CETP.
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