Human cholesteryl ester transport protein transgene promotes macrophage reverse cholesterol transport in C57BL/6 mice and phospholipid transfer protein gene knockout mice

被引:6
|
作者
Liu, Na [1 ]
Si, Yanhong [2 ,3 ]
Zhang, Ying [2 ,3 ]
Guo, Shoudong [1 ,2 ,3 ]
Qin, Shucun [1 ]
机构
[1] Weifang Med Univ, Inst Lipid Metab & Atherosclerosis, Sch Pharm, Innovat Drug Res Ctr, Weifang 261053, Peoples R China
[2] Shandong First Med Univ, Inst Atherosclerosis, Key Lab Atherosclerosis Univ Shandong Prov, Tai An 271000, Shandong, Peoples R China
[3] Shandong Acad Med Sci, Tai An 271000, Shandong, Peoples R China
关键词
Isotope tracing; Transgenic mice; Reverse cholesterol transport; Lipoprotein; LC-MS; MS; HIGH-DENSITY-LIPOPROTEIN; A-I METABOLISM; APOLIPOPROTEIN-E; RECEPTOR; CETP; EXPRESSION; ATHEROSCLEROSIS; EFFLUX; HDL; DEFICIENCY;
D O I
10.1007/s13105-021-00834-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 x PLTP KO mice were obtained after several generations of reproduction. The efficiency of RCT was detected using [H-3]-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-3]-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.
引用
收藏
页码:683 / 694
页数:12
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