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Journal of Lipid Research, Vol. 43, 1875-1880, November 2002
Copyright © 2002 by Lipid Research, Inc.

Elevation of plasma phospholipid transfer protein in transgenic mice increases VLDL secretion

Jessica Lie^*, Rini de Crom^,, Teus van Gent^*, Rien van Haperen, Leo Scheek^*, Inge Lankhuizen^* and Arie van Tol^1,*

^* Departments of Biochemistry, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands
Cell Biology and Genetics, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands
Vascular Surgery, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands

¹ To whom correspondence should be addressed. e-mail: vantol{at}bc1.fgg.eur.nl

Two 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 µg/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.

Supplementary key words PLTP • CETP • transgenic mice • VLDL

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