Liu Na, Si Yanhong, Zhang Ying, Guo Shoudong, Qin Shucun
Institute of Lipid Metabolism and Atherosclerosis, Innovative Drug Research Centre, School of Pharmacy, Weifang Medical University, Weifang, 261053, China.
Key Laboratory of Atherosclerosis in Universities of Shandong Province, Institute of Atherosclerosis, Shandong First Medical University & Shandong Academy of Medical Sciences, Taian, 271000, China.
J Physiol Biochem. 2021 Nov;77(4):683-694. doi: 10.1007/s13105-021-00834-9. Epub 2021 Aug 17.
Cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) belong to the same gene family. Liver-specific expression of CETP improves reverse cholesterol transport (RCT) and PLTP knockout (KO) decreases RCT in mice. In this study, we investigate the effect of CETP transgene (CETP-tg) on RCT and whether CETP-tg can partially restore RCT efficiency in PLTP KO mice. Several rounds of crossing were carried out to produce colonies of wild type (WT), CETP-tg, PLTP KO, and CETP-tg × PLTP KO mice were obtained after several generations of reproduction. The efficiency of RCT was detected using [H]-cholesterol-laden macrophages, and the underlying mechanisms were investigated by multiple techniques. Our data demonstrated that CETP-tg significantly increased the transport rate of [H]-cholesterol from macrophages to plasma and liver, and finally the excretion through feces compared to the WT littermates. The RCT improving effect of CETP-tg was similar in PLTPKO mice. Furthermore, CETP-tg did not affect the expression of RCT-related proteins, such as low-density lipoprotein receptor. The mechanisms of improving RCT may be attributed to the low level of oxidized lipids in CETP-tg mouse and CETP-mediated lipid transport. Collectively, CETP-tg improves RCT in mice, and CETP can not compensate for PLTP deficiency.
胆固醇酯转运蛋白（CETP）和磷脂转运蛋白（PLTP）属于同一基因家族。在小鼠中，肝脏特异性表达CETP可改善逆向胆固醇转运（RCT），而敲除PLTP（PLTP KO）则会降低RCT。在本研究中，我们探究了CETP转基因（CETP-tg）对RCT的影响，以及CETP-tg是否能部分恢复PLTP KO小鼠的RCT效率。进行了多轮杂交以产生野生型（WT）、CETP-tg、PLTP KO的群体，经过几代繁殖后获得了CETP-tg×PLTP KO小鼠。使用[H] - 载脂蛋白胆固醇的巨噬细胞检测RCT效率，并通过多种技术研究其潜在机制。我们的数据表明，与野生型同窝小鼠相比，CETP-tg显著提高了[H] - 胆固醇从巨噬细胞到血浆和肝脏的转运速率，最终通过粪便排出。CETP-tg对RCT 的改善作用在PLTP KO小鼠中相似。此外，CETP-tg不影响RCT相关蛋白如低密度脂蛋白受体的表达。改善RCT的机制可能归因于CETP-tg小鼠中氧化脂质水平较低以及CETP介导的脂质转运。总体而言，CETP-tg可改善小鼠的RCT，且CETP无法弥补PLTP缺陷。
