Cholesteryl ester transfer protein (CETP) expression enhances HDL cholesteryl ester liver delivery, which is independent of scavenger receptor BI, LDL receptor related protein and possibly LDL receptor.
Cholesteryl ester transfer protein (CETP) expression enhances HDL cholesteryl ester liver delivery, which is independent of scavenger receptor BI, LDL receptor related protein and possibly LDL receptor.
复制标题
DOI：
10.1016/j.bbalip.2006.09.008
复制
发表时间：
2006-12
期刊：
影响因子：
--
通讯作者：
Hongwen Zhou;Zhiqiang Li;D. Silver;Xian-Cheng Jiang
中科院分区：
文献类型：
--
作者：
Hongwen Zhou;Zhiqiang Li;D. Silver;Xian-Cheng Jiang
胆固醇酯转移蛋白（CETP）是一种疏水血浆糖蛋白，介导胆固醇酯（CE）和甘油三酯（TG）在血浆脂蛋白之间的转移和交换，在HDL代谢中也起重要作用。先前的研究表明，与野生型小鼠相比，人CETP转基因小鼠的血浆HDL CE水平显著降低，这与肝脏对HDL CE的摄取增强有关。然而，这一过程的机制尚不清楚。为了评估CETP直接介导的可能性，我们利用CETP转基因（CETPTg）小鼠肝清除率受体BI （SR-BI）缺乏[即PDZK1基因敲除（pdzk10）]和受体相关蛋白（RAP）过表达，阻断LDL受体相关蛋白（LRP）和LDL受体（LDLR）。我们发现(1)CETPTg/ pdzk10小鼠的HDL-C明显低于PDZK1 KO小鼠（36%,p<0.01）；(2) CETPTg和CETPTg/ pdzk10小鼠的HDL-C水平相同；(3) CETPTg/ pdzk10 /RAP小鼠血浆HDL-C水平显著低于pdzk10 /RAP小鼠（50%,p<0.001）；(4)在表达CETP的小鼠体内，高密度脂蛋白CE的放射性没有向含载脂蛋白b的脂蛋白部分增加转移；(5) CETPTg/ pdzk10 /RAP小鼠血浆和肝脏[3H]CEt-HDL周转率显著高于pdzk10 /RAP小鼠（分别为50%和53%，p<0.01）。这些结果表明，小鼠体内CETP的表达增加了肝脏中高密度脂蛋白CE的直接清除，这一过程与SR-BI、LRP和LDLR无关。
Cholesteryl ester transfer protein (CETP) is a hydrophobic plasma glycoprotein that mediates the transfer and exchange of cholesteryl ester (CE) and triglyceride (TG) between plasma lipoproteins, and also plays an important role in HDL metabolism. Previous studies have indicated that, compared to wild type mice, human CETP transgenic mice had significantly lower plasma HDL CE levels, which was associated with enhancement of HDL CE uptake by the liver. However, the mechanism of this process is still unknown. To evaluate the possibility that this might be directly mediated by CETP, we utilized CETP transgenic (CETPTg) mice with liver scavenger receptor BI (SR-BI) deficiency [i.e., PDZK1 gene knockout (PDZK1O)], and with receptor associated protein (RAP) overexpression, to block LDL receptor-related protein (LRP) and LDL receptor (LDLR). We found that (1) CETPTg/PDZK1O mice have significantly lower HDL-C than that of PDZK1 KO mice (36%, p<0.01); (2) CETPTg and CETPTg/PDZK1O mice have same HDL-C levels; (3) CETPTg/PDZK1O/RAP mice had significant lower plasma HDL-C levels than that of PDZK1O/RAP ones (50%, p<0.001); (4) there is no incremental transfer of HDL CE radioactivity to the apoB-containing lipoprotein fraction in mice expressing CETP; and (5) CETPTg/PDZK1O/RAP mice had significant higher plasma and liver [3H]CEt-HDL turnover rates than that of PDZK1O/RAP ones (50% and 53%, p<0.01, respectively). These results suggest that CETP expression in mouse increases direct removal of HDL CE in the liver and this process is independent of SR-BI, LRP, and possibly LDLR.