Department of Pathology, The University of Chicago, Chicago, IL, USA.
Ben May Department, The University of Chicago, Chicago, IL, USA.
Methods Mol Biol. 2022;2419:379-411. doi: 10.1007/978-1-0716-1924-7_24.
Atherosclerosis is a chronic inflammatory disorder that is the underlying cause of most cardiovascular disease. Resident cells of the artery wall and cells of the immune system participate in atherogenesis. This process is influenced by plasma lipoproteins, genetics, and the hemodynamics of the blood flow in the artery. A variety of animal models have been used to study the pathophysiology and mechanisms that contribute to atherosclerotic lesion formation. No model is ideal as each has its own advantages and limitations with respect to manipulation of the atherogenic process and modeling human atherosclerosis and lipoprotein profile. In this chapter we will discuss pig and mouse models of experimental atherosclerosis. The similarity of pig lipoprotein metabolism and the pathophysiology of the lesions in these animals with that of humans is a major advantage. While a few genetically engineered pig models have been generated, the ease of genetic manipulation in mice and the relatively short time frame for the development of atherosclerosis has made them the most extensively used model. Newer approaches to induce hypercholesterolemia in mice have been developed that do not require germline modifications. These approaches will facilitate studies on atherogenic mechanisms.
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。动脉壁的固有细胞和免疫系统细胞参与动脉粥样硬化的形成。这一过程受到血浆脂蛋白、遗传因素和动脉血流动力学的影响。已经使用了多种动物模型来研究促进动脉粥样硬化病变形成的病理生理学和机制。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过程和模拟人类动脉粥样硬化和脂蛋白谱方面都有其自身的优点和局限性。在这一章中，我们将讨论实验性动脉粥样硬化的猪和小鼠模型。猪脂蛋白代谢及其病变的病理生理学与人类相似是一个主要优势。虽然已经产生了少数几种基因工程猪模型，但由于小鼠的遗传操作更容易，以及动脉粥样硬化发展的相对较短时间框架，使得它们成为最广泛使用的模型。已经开发出了一些新的诱导小鼠高胆固醇血症的方法，这些方法不需要对生殖系进行修饰。这些方法将有助于研究动脉粥样硬化的发病机制。
