Genomic and Transcriptomic Analysis of Hypercholesterolemic Rabbits: Progress and Perspectives.
Genomic and Transcriptomic Analysis of Hypercholesterolemic Rabbits: Progress and Perspectives.
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高胆固醇血症兔的基因组和转录组分析：进展与展望
DOI：
10.3390/ijms19113512
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发表时间：
2018-11-08
影响因子：
5.6
通讯作者：
Liang J
中科院分区：
文献类型：
--
作者：
Fan J;Chen Y;Yan H;Liu B;Wang Y;Zhang J;Chen YE;Liu E;Liang J
家兔（Oryctolagus cuniculus）是研究人类脂质代谢和动脉粥样硬化的最广泛使用的动物模型之一，因为它们比其他实验动物如啮齿动物对胆固醇饮食更敏感。目前，两种高胆固醇血症兔模型经常用于动脉粥样硬化研究。一个是胆固醇喂养的野生型兔，另一个是渡边遗传性高脂血症（WHHL）兔，这是遗传缺陷的低密度脂蛋白（LDL）受体功能。野生型家兔在高胆固醇饮食条件下容易发生严重的高胆固醇血症，这是由于肝脏和肝脏来源的残余脂蛋白（称为β-极低密度脂蛋白（VLDL），富含胆固醇酯）显著增加。WHHL兔的特征在于在标准食物饮食中血浆LDL水平升高，这类似于人类家族性高胆固醇血症。因此，这两种兔模型均发生主动脉和冠状动脉粥样硬化，但血浆胆固醇水平升高是由完全不同的机制引起的。此外，胆固醇喂养的兔而不是WHHL兔表现出不同程度的脂肪肝。最近，我们沿着与其他人已经表明，有许多差异表达的基因在动脉粥样硬化病变和肝脏的胆固醇喂养的兔子，无论是显着上调或下调，与那些在正常的兔子，包括基因参与调节炎症和脂质代谢。因此，膳食胆固醇不仅在高胆固醇血症和动脉粥样硬化中起重要作用，而且在脂肪肝中也起重要作用。本文就高胆固醇血症家兔的基因组学和转录组学研究进展作一综述。这些转录组学分析数据将为高胆固醇血症与动脉粥样硬化或饮食胆固醇引起的肝功能障碍之间的关系提供新的见解。
Rabbits (Oryctolagus cuniculus) are one of the most widely used animal models for the study of human lipid metabolism and atherosclerosis because they are more sensitive to a cholesterol diet than other experimental animals such as rodents. Currently, two hypercholesterolemic rabbit models are frequently used for atherosclerosis studies. One is a cholesterol-fed wild-type rabbit and the other is the Watanabe heritable hyperlipidemic (WHHL) rabbit, which is genetically deficient in low density lipoprotein (LDL) receptor function. Wild-type rabbits can be easily induced to develop severe hypercholesterolemia with a cholesterol-rich diet due to the marked increase in hepatically and intestinally derived remnant lipoproteins, called β-very low density lipoproteins (VLDL), which are rich in cholesteryl esters. WHHL rabbits are characterized by elevated plasma LDL levels on a standard chow diet, which resembles human familial hypercholesterolemia. Therefore, both rabbit models develop aortic and coronary atherosclerosis, but the elevated plasma cholesterol levels are caused by completely different mechanisms. In addition, cholesterol-fed rabbits but not WHHL rabbits exhibit different degrees of hepatosteatosis. Recently, we along with others have shown that there are many differentially expressed genes in the atherosclerotic lesions and livers of cholesterol-fed rabbits that are either significantly up- or down-regulated, compared with those in normal rabbits, including genes involved in the regulation of inflammation and lipid metabolism. Therefore, dietary cholesterol plays an important role not only in hypercholesterolemia and atherosclerosis but also in hepatosteatosis. In this review, we make an overview of the recent progress in genomic and transcriptomic analyses of hypercholesterolemic rabbits. These transcriptomic profiling data should provide novel insight into the relationship between hypercholesterolemia and atherosclerosis or hepatic dysfunction caused by dietary cholesterol.
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影响因子：
15.9
作者：
GALIS, ZS;SUKHOVA, GK;LIBBY, P
通讯作者：
LIBBY, P
影响因子：
4.5
作者：
Ning B;Wang X;Yu Y;Waqar AB;Yu Q;Koike T;Shiomi M;Liu E;Wang Y;Fan J
通讯作者：
Fan J
DOI：
10.1073/pnas.0506201102
发表时间：
2005-10-25
影响因子：
11.1
作者：
Johnson, JL;George, SJ;Jackson, CL
通讯作者：
Jackson, CL
影响因子：
37.8
作者：
Liang, JY;Liu, EQ;Fan, JL
通讯作者：
Fan, JL
影响因子：
3.7
作者：
Bai L;Li Q;Li L;Lin Y;Zhao S;Wang W;Wang R;Li Y;Yuan J;Wang C;Wang Z;Fan J;Liu E
通讯作者：
Liu E