Department of Pathology, University of Chicago, Chicago, IL 60637, USA.
Arterioscler Thromb Vasc Biol. 2012 May;32(5):1104-15. doi: 10.1161/ATVBAHA.111.237693. Epub 2012 Mar 1.
Atherosclerosis is a chronic inflammatory disorder that is the underlying cause of most cardiovascular disease. Both cells of the vessel wall and cells of the immune system participate in atherogenesis. This process is heavily influenced by plasma lipoproteins, genetics, and the hemodynamics of the blood flow in the artery. A variety of small and large animal models have been used to study the atherogenic process. No model is ideal as each has its own advantages and limitations with respect to manipulation of the atherogenic process and modeling human atherosclerosis or lipoprotein profile. Useful large animal models include pigs, rabbits, and nonhuman primates. Due in large part to the relative ease of genetic manipulation and the relatively short time frame for the development of atherosclerosis, murine models are currently the most extensively used. Although not all aspects of murine atherosclerosis are identical to humans, studies using murine models have suggested potential biological processes and interactions that underlie this process. As it becomes clear that different factors may influence different stages of lesion development, the use of mouse models with the ability to turn on or delete proteins or cells in tissue specific and temporal manner will be very valuable.
动脉粥样硬化是一种慢性炎症性疾病,是大多数心血管疾病的根本原因。血管壁细胞和免疫系统细胞都参与动脉粥样硬化的形成。这个过程受到血浆脂蛋白、遗传和动脉血流动力学的强烈影响。已经使用了多种小型和大型动物模型来研究动脉粥样硬化的形成过程。没有一种模型是理想的,因为每种模型在操纵动脉粥样硬化形成过程和模拟人类动脉粥样硬化或脂蛋白谱方面都有其自身的优点和局限性。有用的大型动物模型包括猪、兔子和非人类灵长类动物。在很大程度上由于遗传操作相对容易,以及动脉粥样硬化发展的时间框架相对较短,鼠类模型目前是使用最广泛的。虽然鼠类动脉粥样硬化的所有方面都与人类不完全相同,但使用鼠类模型的研究表明了潜在的生物学过程和相互作用,这些过程是导致动脉粥样硬化的基础。随着人们越来越清楚地认识到不同的因素可能会影响病变发展的不同阶段,使用具有在组织特异性和时间性上开启或删除蛋白质或细胞的能力的小鼠模型将非常有价值。