van Haperen Rien, van Tol Arie, van Gent Teus, Scheek Leo, Visser Pim, van der Kamp Arthur, Grosveld Frank, de Crom Rini
Department of Cell Biology & Genetics, Erasmus Medical Center, 3000 DR Rotterdam, The Netherlands.
J Biol Chem. 2002 Dec 13;277(50):48938-43. doi: 10.1074/jbc.M209128200. Epub 2002 Oct 7.
Plasma phospholipid transfer protein (PLTP) is thought to be involved in the remodeling of high density lipoproteins (HDL), which are atheroprotective. It is also involved in the metabolism of very low density lipoproteins (VLDL). Hence, PLTP is thought to be an important factor in lipoprotein metabolism and the development of atherosclerosis. We have overexpressed PLTP in mice heterozygous for the low density lipoprotein (LDL) receptor, a model for atherosclerosis. We show that increased PLTP activity results in a dose-dependent decrease in HDL, and a moderate stimulation of VLDL secretion (</=1.5-fold). The mice were given a high fat, high cholesterol diet, which resulted in hypercholesterolemia in all animals. HDL concentrations were dramatically reduced in PLTP-overexpressing animals when compared with LDL receptor controls, whereas VLDL + LDL cholesterol levels were identical. Susceptibility to atherosclerosis was increased in a PLTP dose-responsive manner. We conclude that PLTP increases susceptibility to atherosclerosis by lowering HDL concentrations, and therefore we suggest that an increase in PLTP is a novel, long term risk factor for atherosclerosis in humans.
血浆磷脂转运蛋白（PLTP）被认为参与了具有抗动脉粥样硬化作用的高密度脂蛋白（HDL）的重塑过程。它还参与极低密度脂蛋白（VLDL）的代谢。因此，PLTP被认为是脂蛋白代谢和动脉粥样硬化发展中的一个重要因素。我们在低密度脂蛋白（LDL）受体杂合的小鼠中过表达了PLTP，该小鼠是动脉粥样硬化的模型。我们发现，PLTP活性增加导致HDL呈剂量依赖性降低，以及VLDL分泌受到适度刺激（≤1.5倍）。给这些小鼠喂食高脂肪、高胆固醇饮食，所有动物均出现高胆固醇血症。与LDL受体对照相比，PLTP过表达动物的HDL浓度显著降低，而VLDL + LDL胆固醇水平相同。对动脉粥样硬化的易感性以PLTP剂量反应性方式增加。我们得出结论，PLTP通过降低HDL浓度增加了对动脉粥样硬化的易感性，因此我们认为PLTP升高是人类动脉粥样硬化的一个新的长期危险因素。
