Apolipoprotein E deficiency accelerates atherosclerosis development in miniature pigs.
Apolipoprotein E deficiency accelerates atherosclerosis development in miniature pigs.
复制标题
载脂蛋白E缺乏加速小型猪动脉粥样硬化的发展
DOI：
10.1242/dmm.036632
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发表时间：
2018-10-10
影响因子：
4.3
通讯作者：
Dai Y
中科院分区：
文献类型：
--
作者：
Fang B;Ren X;Wang Y;Li Z;Zhao L;Zhang M;Li C;Zhang Z;Chen L;Li X;Liu J;Xiong Q;Zhang L;Jin Y;Liu X;Li L;Wei H;Yang H;Li R;Dai Y
小型猪在动脉粥样硬化建模方面比啮齿动物具有优势，因为它们的心血管系统和生理机能与人类相似。载脂蛋白E（ApoE）缺乏长期以来一直与人类心血管疾病有关。为了建立一种改良的家族性高胆固醇血症和动脉粥样硬化大型动物模型，利用规律成簇的间隔短回文重复序列（CRISPR）相关蛋白9系统（CRISPR/Cas9）破坏巴马小型猪的ApoE基因。同时产生了具有框内突变（ApoEm/m）和移码突变（ApoE−/−）的双等位基因修饰的ApoE猪。ApoE−/−猪在饲喂常规饲料时血浆胆固醇水平适度升高，但在高脂高胆固醇（HFHC）饮食喂养6个月后，表现出严重的高胆固醇血症，并在主动脉和冠状动脉自发形成类似人类的动脉粥样硬化病变。因此，这些ApoE−/−猪可能是有价值的大型动物模型，可为动脉粥样硬化的转化研究提供更深入的见解。
编辑推荐：ApoE基因敲除猪在高脂高胆固醇饮食喂养6个月内表现出严重的高胆固醇血症，并在主动脉和冠状动脉自发形成类似人类的动脉粥样硬化病变。
ABSTRACT Miniature pigs have advantages over rodents in modeling atherosclerosis because their cardiovascular system and physiology are similar to that of humans. Apolipoprotein E (ApoE) deficiency has long been implicated in cardiovascular disease in humans. To establish an improved large animal model of familial hypercholesterolemia and atherosclerosis, the clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 system (CRISPR/Cas9) was used to disrupt the ApoE gene in Bama miniature pigs. Biallelic-modified ApoE pigs with in-frame mutations (ApoEm/m) and frameshift mutations (ApoE−/−) were simultaneously produced. ApoE−/− pigs exhibited moderately increased plasma cholesterol levels when fed with a regular chow diet, but displayed severe hypercholesterolemia and spontaneously developed human-like atherosclerotic lesions in the aorta and coronary arteries after feeding on a high-fat and high-cholesterol (HFHC) diet for 6 months. Thus, these ApoE−/− pigs could be valuable large animal models for providing further insight into translational studies of atherosclerosis. Editor's choice: ApoE knockout pigs displayed severe hypercholesterolemia and spontaneously developed human-like atherosclerotic lesions in the aorta and coronary arteries within 6 months of feeding on a high-fat and high-cholesterol diet.
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影响因子：
56.9
作者：
MAHLEY, RW
通讯作者：
MAHLEY, RW
影响因子：
11
作者：
Davies G;Harris SE;Reynolds CA;Payton A;Knight HM;Liewald DC;Lopez LM;Luciano M;Gow AJ;Corley J;Henderson R;Murray C;Pattie A;Fox HC;Redmond P;Lutz MW;Chiba-Falek O;Linnertz C;Saith S;Haggarty P;McNeill G;Ke X;Ollier W;Horan M;Roses AD;Ponting CP;Porteous DJ;Tenesa A;Pickles A;Starr JM;Whalley LJ;Pedersen NL;Pendleton N;Visscher PM;Deary IJ
通讯作者：
Deary IJ
影响因子：
5.4
作者：
Li Y;Fuchimoto D;Sudo M;Haruta H;Lin QF;Takayama T;Morita S;Nochi T;Suzuki S;Sembon S;Nakai M;Kojima M;Iwamoto M;Hashimoto M;Yoda S;Kunimoto S;Hiro T;Matsumoto T;Mitsumata M;Sugitani M;Saito S;Hirayama A;Onishi A
通讯作者：
Onishi A
影响因子：
64.5
作者：
Hsu PD;Lander ES;Zhang F
通讯作者：
Zhang F
影响因子：
5.9
作者：
Chen, Fengjiao;Wang, Ying;Dai, Yifan
通讯作者：
Dai, Yifan