Anatomical differences and atherosclerosis in apolipoprotein E-deficient mice with 129/SvEv and C57BL/6

Anatomical differences and atherosclerosis in apolipoprotein E-deficient mice with 129/SvEv and C57BL/6
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DOI:
10.1016/j.atherosclerosis.2006.12.006
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发表时间:
2007-11-01
期刊:
影响因子:
5.3
通讯作者:
Reddick, Robert
Reddick, Robert
中科院分区:
医学2区
文献类型:
--
作者:
Maeda, Nobuyo;Johnson, Lance;Reddick, Robert

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众所周知,遗传背景对小鼠动脉粥样硬化的易感性有影响,为了研究这些影响的基础,我们在129/SvEv来源的小鼠胚胎干细胞中产生了载脂蛋白E零突变,并将其保持在近交系(129-apoE)中,并将这些小鼠与以前培育的129/O1a系和回交到C57BL/6遗传背景(B6-apoE)的小鼠进行了比较。ApoE-129小鼠的血浆胆固醇和甘油三酯水平是apoE-B6小鼠的两倍,极低密度脂蛋白/乳糜粒残留物和高密度脂蛋白颗粒都增加了。斑块大小与小鼠年龄的回归分析表明,129-apoE小鼠主动脉根部动脉粥样硬化斑块的开始发展(雌性为3.9月,雄性为4.1月)慢于B6-apoE小鼠(雌性为1.3个月,雄性为2.8个月)。相比之下,129-apoE小鼠在主动脉中形成广泛的斑块:弓形早于136-apoE小鼠。两个品系之间主动脉弓几何形状的明显差异表明,解剖学上的差异可能有助于遗传背景对动脉粥样硬化的影响。因此,129-apoE/B6-apoE对为研究控制动脉几何形状和斑块形成位置之间关系的因素提供了一种工具。(C)2006爱思唯尔爱尔兰有限公司。保留所有权利。
There are well-known genetic background effects on atherosclerosis susceptibility in mice, To study the basis of these effects, we have generated the apolipoprotein E-null mutation in mouse embryonic stem cells of 129/SvEv origin, maintained it in the inbred strain (129-apoE), and compared these mice with those previously made in strain 129/Ola and backcrossed to a C57BL/6 genetic background (B6-apoE). Plasma cholesterol and triglyceride levels in the apoE-129 mice are twice the levels in apoE-B6, and both VLDL/chylomicron remnants and HDL particles are increased. Regression analysis of plaque size relative to the age of mice suggests that the initiation of atherosclerotic plaque development at the aortic root is slower in 129-apoE mice (intercept at 3.9 months in females and 4.1 months in males) than in B6-apoE mice (1.3 months in females and 2.8 months in males). In contrast, 129-apoE mice develop extensive plaques in the aortic: arches earlier than 136-apoE mice. Distinct differences in the geometry of the aortic arch between the two strains suggest that anatomical differences may contribute to the effects of genetic background on atherosclerosis. The 129-apoE/B6-apoE pair thus provides a tool to study factors governing the relation between arterial geometry and the location of plaque development. (c) 2006 Elsevier Ireland Ltd. All rights reserved.