Reduced high density lipoprotein cholesterol in human cholesteryl ester transfer protein transgenic mice.

Reduced high density lipoprotein cholesterol in human cholesteryl ester transfer protein transgenic mice.
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DOI:
10.1016/s0021-9258(18)99088-5
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发表时间:
1991-06
期刊:
The Journal of biological chemistry
影响因子:
--
通讯作者:
L. Agellon;A. Walsh;T. Hayek;P. Moulin;Xian-Cheng Jiang;S. Shelanski;J. Breslow;A. Tall
L. Agellon;A. Walsh;T. Hayek;P. Moulin;Xian-Cheng Jiang;S. Shelanski;J. Breslow;A. Tall
中科院分区:
其他
文献类型:
--
作者:
L. Agellon;A. Walsh;T. Hayek;P. Moulin;Xian-Cheng Jiang;S. Shelanski;J. Breslow;A. Tall

文献摘要

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人胆固醇酯转移蛋白(CETP)促进脂蛋白之间的中性脂质交换。为了评估血浆CETP增加对脂蛋白水平的影响,将人CETP小基因置于小鼠金属硫蛋白-I启动子的控制下,并用于开发转基因小鼠。将人CETP转基因整合到小鼠基因组中导致活性血浆CETP的产生。锌诱导CETP转基因表达引起抑郁症的血清胆固醇由于显着降低高密度脂蛋白胆固醇。极低和低密度脂蛋白中总胆固醇含量无变化。然而,血浆和转基因小鼠血浆中所有脂蛋白组分中游离胆固醇/胆固醇酯比率降低,表明刺激血浆胆固醇酯化。结果表明,高水平的血浆CETP活性可能是人体高密度脂蛋白减少的原因。
The human cholesteryl ester transfer protein (CETP) facilitates the exchange of neutral lipids among lipoproteins. In order to evaluate the effects of increased plasma CETP on lipoprotein levels, a human CETP minigene was placed under the control of the mouse metallothionein-I promoter and used to develop transgenic mice. Integration of the human CETP transgene into the mouse genome resulted in the production of active plasma CETP. Zinc induction of CETP transgene expression caused depression of serum cholesterol due to a significant reduction of high density lipoprotein cholesterol. There was no change in total cholesterol content in very low and low density lipoproteins. However, there was a decrease in the free cholesterol/cholesteryl ester ratio in plasma and in all lipoprotein fractions of transgenic mouse plasma, suggesting stimulation of plasma cholesterol esterification. The results suggest that high levels of plasma CETP activity may be a cause of reduced high density lipoproteins in humans.