Hypertriglyceridemia and delayed clearance of fat load in transgenic rabbits expressing human apolipoprotein CIII

被引：33
作者：
Ding, Yinyuan [1 ,2 ]
Wang, Yuhui [1 ,2 ]
Zhu, Hong [3 ]
Fan, Jianglin [4 ]
Yu, Liqing [5 ]
Liu, George [1 ,2 ]
Liu, Enqi [3 ]
机构：
[1] Peking Univ, Inst Cardiovasc Sci, Hlth Sci Ctr, Beijing 100191, Peoples R China
[2] Peking Univ, Key Lab Mol Cardiovasc Sci, Minist Educ, Hlth Sci Ctr, Beijing 100191, Peoples R China
[3] Xi An Jiao Tong Univ, Lab Anim Ctr, Xian 710061, Peoples R China
[4] Univ Yamanashi, Dept Mol Pathol, Interdisciplinary Grad Sch Med & Engn, Yamanashi 4093898, Japan
[5] Wake Forest Univ, Dept Pathol, Sect Lipid Sci, Sch Med, Winston Salem, NC 27157 USA
来源：
TRANSGENIC RESEARCH | 2011年 / 20卷 / 04期
基金：
北京市自然科学基金;
关键词：
Apolipoprotein CIII; Transgenic rabbit; Hypertriglyceridemia; DENSITY-LIPOPROTEIN CHOLESTEROL; DIET-INDUCED OBESITY; IV GENE-CLUSTER; C-III; APOC-III; HYPERLIPOPROTEINEMIA FAILS; ENDOTHELIAL-CELLS; MONOCYTIC CELLS; LIPASE ACTIVITY; LIPID PROFILE;
D O I：
10.1007/s11248-010-9467-5
中图分类号：
Q5 [生物化学];
学科分类号：
071010 ; 081704 ;
摘要：
Apolipoprotein CIII (apoCIII) has been implicated in hypertriglyceridemia and plasma apoCIII independently predicts risk for coronary heart disease. While hypertriglyceridemia in patients has been demonstrated to correlate with elevated plasma apoCIII levels and reduced lipoprotein lipase (LPL) activity, apoCIII transgenic mice show elevated LPL activity. In this study, we generated transgenic (Tg) rabbits expressing human apoCIII gene exclusively in liver and investigated the effect of apoCIII overexpression on lipid metabolism of rabbits. In comparison with non-Tg littermates, Tg rabbits had 3- and 3.2-fold increases in fed and fasted plasma triglycerides, respectively. In contrast, no significant differences were observed in plasma total cholesterol and high density lipoprotein cholesterol levels between Tg and non-Tg rabbits. Analysis of lipoprotein fractions revealed that elevated plasma triglyceride levels in Tg rabbits were mainly attributed to an increase in very low density lipoprotein/chylomicron-sized particles. Furthermore, Tg rabbits showed markedly delayed clearance of plasma triglycerides accompanied with significantly reduced LPL activity in post-heparin plasma compared to that in non-Tg controls. In conclusion, these results indicate apoCIII transgenic rabbits develop hypertriglyceridemia with similar mechanism in hypertriglyceridemic patients via delayed clearance of plasma triglycerides, and could be used as a valuable tool for the study of human hyperlipidemia in relation with atherosclerotic disorders.
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收藏
页码：867 / 875
页数：9
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