Overexpression of human apolipoprotein B-100 in transgenic rabbits results in increased levels of LDL and decreased levels of HDL.
Overexpression of human apolipoprotein B-100 in transgenic rabbits results in increased levels of LDL and decreased levels of HDL.
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DOI：
10.1161/01.atv.15.11.1889
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发表时间：
1995-11
期刊：
影响因子：
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通讯作者：
Jianglin Fan;S. Mccormick;R. Krauss;S. Taylor;Ricky Quan;John Taylor;S. Young
中科院分区：
文献类型：
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作者：
Jianglin Fan;S. Mccormick;R. Krauss;S. Taylor;Ricky Quan;John Taylor;S. Young
在本研究中，使用跨越人apoB基因的80-kb人基因组DNA片段来产生表达人apoB-100的转基因新西兰白色兔。转基因兔血浆中人apoB的浓度范围为5 - 100 mg/dL。与非转基因对照组相比，转基因兔子的血浆甘油三酯和胆固醇水平升高了近三倍。血浆中几乎所有的胆固醇和人apoB都位于LDL部分中。LDL组分的显著甘油三酯富集是转基因兔中人apoB过表达的显著特征，其中LDL组分含有超过75%的血浆甘油三酯。富含磷脂酰肌醇的LDL颗粒比天然兔LDL更小、更致密，并且含有显著增加的apoE和apoC-III。在非转基因对照动物中，大多数甘油三酯在VLDL中，大多数apoE和apoC-III在VLDL和HDL组分中。除了增加LDL水平外，人apoB在兔中的过表达导致HDL胆固醇和apoA-I的血浆水平降低。在我们先前对表达人apoB的转基因小鼠的研究中，我们记录了富含甘油三酯的LDL和降低的HDL胆固醇水平。这些先前在小鼠中的发现，以及目前在转基因兔中的发现，表明富含甘油三酯的LDL和HDL胆固醇水平降低可能是apoB过表达的标志性特征。
In this study, and 80-kb human genomic DNA fragment spanning the human apoB gene was used to generate transgenic New Zealand White rabbits that expressed human apoB-100. The concentration of human apoB in the plasma of the transgenic rabbits ranged between 5 and 100 mg/dL. The transgenic rabbits had nearly threefold elevations in the plasma levels of triglycerides and cholesterol compared with nontransgenic controls. Nearly all the cholesterol and human apoB in the plasma was in the LDL fraction. Pronounced triglyceride enrichment of the LDL fraction was a striking feature of human apoB overexpression in the transgenic rabbits, in which the LDL fraction contained more than 75% of the plasma triglycerides. The triglyceride-enriched LDL particles were smaller and more dense than the native rabbit LDL and contained markedly increased amounts of apoE and apoC-III. In the nontransgenic control animals most of the triglycerides were in the VLDL, and most of the apoE and apoC-III were in the VLDL and HDL fractions. In addition to increased LDL levels, overexpression of human apoB in rabbits resulted in lower plasma levels of HDL cholesterol and apoA-I. In our prior studies on transgenic mice expressing human apoB, we documented triglyceride-rich LDL and reduced levels of HDL cholesterol. These prior findings in mice, together with the present findings in transgenic rabbits, suggest that triglyceride-rich LDL and lowered levels of HDL cholesterol may be hallmark features of apoB overexpression.