Lie Jessica, de Crom Rini, van Gent Teus, van Haperen Rien, Scheek Leo, Lankhuizen Inge, van Tol Arie
Department of Biochemistry, Erasmus Medical Center, PO Box 1738, 3000 DR Rotterdam, The Netherlands.
J Lipid Res. 2002 Nov;43(11):1875-80. doi: 10.1194/jlr.m200166-jlr200.
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.
两种脂质转运蛋白在人血浆中具有活性，即胆固醇酯转运蛋白（CETP）和磷脂转运蛋白（PLTP）。小鼠天然不表达CETP。PLTP基因的额外失活导致极低密度脂蛋白（VLDL）分泌减少，随后对饮食诱导的动脉粥样硬化的易感性降低。本研究的目的是评估PLTP表达差异对CETP和PLTP功能正常的小鼠中VLDL分泌的可能影响。我们将人CETP转基因（huCETPtg）小鼠与表达两种人脂质转运蛋白的小鼠（huCETPtg/huPLTPtg）进行了比较。与huCETPtg/huPLTPtg小鼠相比，huCETPtg小鼠的血浆胆固醇高1.5倍（P < 0.001）。这种差异主要是由于huCETPtg/huPLTPtg小鼠的高密度脂蛋白（HDL）水平较低，这随后可能导致在huCETPtg/huPLTPtg小鼠中发现的CETP活性和浓度略有降低（P < 0.05）。这些动物的PLTP活性增加了2.8倍（P < 0.001）。人PLTP浓度为5微克/毫升。与huCETPtg小鼠相比，PLTP的适度过表达导致VLDL分泌增加1.5倍（P < 0.05）。两种品系中新生VLDL的组成相似。这些结果表明，huCETPtg小鼠中升高的PLTP活性导致VLDL分泌增加。此外，PLTP过表达会降低血浆HDL胆固醇以及CETP。
