Chen Yung Chih, Rivera Jennifer, Peter Karlheinz
Atherothrombosis and Vascular Biology, Baker IDI Heart and Diabetes Institute, St Kilda Road Central, 6492, Melbourne, VIC, 8008, Australia.
Departments of Medicine and Immunology, Monash University, Melbourne, VIC, Australia.
Methods Mol Biol. 2015;1339:333-8. doi: 10.1007/978-1-4939-2929-0_23.
Despite the number of animal models of atherosclerosis, a major limitation in research on mechanisms of plaque rupture is the lack of appropriate atherosclerotic mouse models where lesions develop and progress to a vulnerable and thus rupture-prone phenotype that is typically observed in humans. Most animal models of atherosclerosis typically represent a few but not the full combination of the characteristics seen in human unstable/ruptured plaques. Such characteristics most importantly include a thin and ruptured fibrous cap, plaque inflammation, neovascularization within the plaque (vasa vasorum), plaque hemorrhage, and intravascular (often occlusive) thrombus formation. Ideally, an animal model of plaque instability/rupture would respond to current pharmacological interventions known to reduce the risk of plaque rupture, such as statins. Here we describe a mouse model of plaque instability/rupture that is based on the surgical introduction of a tandem stenosis in the carotid artery. This model results in the formation of unstable atherosclerotic plaques that reflect human plaque pathology. It will allow to further understanding of plaque instability/rupture, to identify the participating factors such as specific proteins, genes and microRNAs, and to develop imaging methods towards the detection of vulnerable, rupture-prone atherosclerotic plaques.
尽管有多种动脉粥样硬化动物模型，但斑块破裂机制研究中的一个主要局限是缺乏合适的动脉粥样硬化小鼠模型，在这类模型中，病变会发展并进展为易损且因此易于破裂的表型，而这种表型通常在人类中观察到。大多数动脉粥样硬化动物模型通常仅体现人类不稳定/破裂斑块中所见特征的一部分，而非全部特征组合。这些特征最重要的包括薄且破裂的纤维帽、斑块炎症、斑块内新生血管形成（滋养血管）、斑块出血以及血管内（通常为闭塞性）血栓形成。理想情况下，斑块不稳定/破裂动物模型应对当前已知可降低斑块破裂风险的药物干预措施（如他汀类药物）产生反应。在此，我们描述一种基于在颈动脉中手术引入串联狭窄建立的斑块不稳定/破裂小鼠模型。该模型会形成反映人类斑块病理的不稳定动脉粥样硬化斑块。它将有助于进一步理解斑块不稳定/破裂，识别诸如特定蛋白质、基因和微小RNA等参与因素，并开发用于检测易损、易于破裂的动脉粥样硬化斑块的成像方法。
