Induction of rapid atherogenesis by perivascular carotid collar placement in apolipoprotein E-deficient and low-density lipoprotein receptor-deficient mice
Induction of rapid atherogenesis by perivascular carotid collar placement in apolipoprotein E-deficient and low-density lipoprotein receptor-deficient mice
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DOI：
10.1161/01.cir.103.8.1164
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发表时间：
2001-02-27
期刊：
影响因子：
37.8
通讯作者：
Biessen, EAL
中科院分区：
文献类型：
--
作者：
von der Thüsen, JH;van Berkel, TJC;Biessen, EAL
背景-血管周围项圈放置已被用作在各种实验动物中诱导局部动脉粥样硬化的手段。然而，在小鼠中，到目前为止还没有通过这种方法获得动脉粥样硬化样病变。方法和结果：在载脂蛋白E缺陷(apoE-/-)和低密度脂蛋白受体缺陷(LDLR-/-)小鼠的颈动脉周围放置硅胶圈。衣领诱导的损伤主要发生在项圈近端，并依赖于高胆固醇饮食，apoE-/-鼠在3周后病变明显，LDLR-/-鼠在6周后病变明显，表现为明显的动脉粥样硬化。在apoE-/-小鼠和LDLR-/-小鼠中，6周后管腔狭窄达到85%和61%，细胞间黏附分子-1和血管细胞黏附分子-1的表达水平在颈圈近端和远端均增加，而内皮一氧化氮合酶在近端的表达下调。结论：颈圈诱导的颈动脉粥样硬化形成加速是血流动力学的原因。它可以作为与动脉粥样硬化的潜在原因和发病机制相关的连续机制研究的底物。病变的快速发展还将有助于有效筛选新的潜在抗动脉粥样硬化的化学实体，并评估有效时间有限的治疗方法，如腺病毒基因治疗。
Background-Perivascular collar placement has been used as a means for localized atherosclerosis induction in a variety of experimental animal species. In mice, however, atherosclerosis-like lesions have thus far not been obtained by this method. The aim of this study was the development of a mouse model of rapid, site-controlled atherogenesis.Methods and Results-Silastic collars were placed around the carotid arteries of apolipoprotein E-deficient (apoE-/-) and LDL receptor-deficient (LDLr-/-) mice. The development of collar-induced lesions was found to occur predominantly in the area proximal to the collar and to be dependent on a high-cholesterol diet, Lesions were evident in apoE-/- mice after 3 weeks and in LDLr-/- mice after 6 weeks and were overtly atherosclerotic in appearance. Lumen stenosis reached 85% in apoE-/- mice and 61% in LDLr-/- mice 6 weeks after collar insertion, Expression levels of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 were increased both proximal and distal to the collar, whereas endothelial nitric oxide synthase expression was downregulated at the proximal site,Conclusions-We propose that this model of collar-induced acceleration of carotid atherogenesis is of hemodynamic cause. It may serve as a substrate for sequential mechanistic studies concerned with the underlying cause and pathogenesis of atherosclerosis. The rapidity of lesion development will also aid the efficient screening of new potentially antiatherogenic chemical entities and the evaluation of therapies with limited duration of effectiveness, such as adenoviral gene therapy.