HDL biology
Overexpressing phospholipid transfer protein raises VLDL secretion 1.5-fold while lowering HDL cholesterol and CETP activity in CETP-transgenic mice (J Lipid Res 2002)
Original title: Elevation of plasma phospholipid transfer protein in transgenic mice increases VLDL secretion
In mice expressing human CETP alone (huCETPtg) versus mice expressing both human CETP and PLTP (huCETPtg/huPLTPtg), plasma cholesterol was 1.5-fold higher in huCETPtg mice (P < 0.001), largely reflecting lower HDL cholesterol in the double-transgenic mice, a change accompanied by decreased CETP activity and concentration (P < 0.05). PLTP activity was 2.8-fold higher in the double-transgenic animals (P < 0.001), with human PLTP concentration reaching 5 microg/ml. Moderate PLTP overexpression increased VLDL secretion 1.5-fold compared with huCETPtg mice alone (P < 0.05), though nascent VLDL composition was similar between strains. The findings indicate that elevated PLTP activity raises VLDL secretion while lowering plasma HDL cholesterol and CETP.
Original abstract
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 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.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.