Animal models of atherosclerosis
Animal models of atherosclerosis
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DOI：
10.1016/j.ejphar.2017.05.010
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发表时间：
2017-12-05
影响因子：
5
通讯作者：
De Meyer, Guido R. Y.
中科院分区：
文献类型：
--
作者：
Veseli, Besa Emini;Perrotta, Paola;De Meyer, Guido R. Y.
动脉粥样硬化的理想动物模型类似于人类的解剖学和病理生理学，并且有可能用于医学和药物研究中，以获得可以推断到人类医学的结果。此外，必须易于获取，可以以合理的成本来维护，易于处理，并与人类分享病变的地形。通常，由于富含胆固醇/西方型饮食，对胆固醇代谢涉及的基因的操纵以及引入动脉粥样硬化的其他风险因素，动脉粥样硬化的动物模型是基于加速的斑块形成。小鼠和兔子模型主要使用，其次是猪和非人类灵长类动物。这些模型中的每一个都有其优点和局限性。小鼠由于其快速繁殖，遗传操作的易于性以及在合理的时间范围内监测动脉粥样硬化的能力，因此已成为研究实验性动脉粥样硬化的主要物种。载脂蛋白E缺陷（APOE（ - / - ））和LDL受体（LDLR）基因敲除小鼠均经常使用，但APOE/LDLR Double-Knockout，ApoE3-Leiden和PCSK9-AAV小鼠在动脉粥样硬化研究中都是有价值的工具。然而，一个巨大的挑战是开发模型，在这种模型中，斑块内的微梗，出血，自发性动脉粥样硬化斑块破裂，心肌梗塞和猝死始终如一地发生。这些特征存在于APOE（ - / - ）FBN1（C01039G +/-）小鼠中，可以用作临床前研究中经过验证的模型，以评估新颖的斑块稳定药物。
An ideal animal model of atherosclerosis resembles human anatomy and pathophysiology and has the potential to be used in medical and pharmaceutical research to obtain results that can be extrapolated to human medicine. Moreover, it must be easy to acquire, can be maintained at a reasonable cost, is easy to handle and shares the topography of the lesions with humans. In general, animal models of atherosclerosis are based on accelerated plaque formation due to a cholesterol-rich/Western-type diet, manipulation of genes involved in the cholesterol metabolism, and the introduction of additional risk factors for atherosclerosis. Mouse and rabbit models have been mostly used, followed by pigs and non-human primates. Each of these models has its advantages and limitations. The mouse has become the predominant species to study experimental atherosclerosis because of its rapid reproduction, ease of genetic manipulation and its ability to monitor atherogenesis in a reasonable time frame. Both Apolipoprotein E deficient (ApoE(-/-)) and LDL-receptor (LDLr) knockout mice have been frequently used, but also ApoE/LDLr double-knockout, ApoE3-Leiden and PCSK9-AAV mice are valuable tools in atherosclerosis research. However, a great challenge was the development of a model in which intra-plaque microvessels, haemorrhages, spontaneous atherosclerotic plaque ruptures, myocardial infarction and sudden death occur consistently. These features are present in ApoE(-/-) Fbn1(C01039G+/-) mice, which can be used as a validated model in pre-clinical studies to evaluate novel plaque-stabilizing drugs.