Chair of Pharmacology, Jagiellonian University School of Medicine, 31-531 Krakow, Grzegorzecka Str. 16, Poland.
Curr Pharm Biotechnol. 2012 Oct;13(13):2435-9.
Although atherosclerosis was previously thought to be mainly a degenerative disease, it is now well ascertained that its pathogenesis is inflammatory. There was a pivotal role of apoE-knockout mice in understanding the inflammatory background of atherosclerosis. Currently, atherosclerosis is known as a chronic inflammatory disease, in most cases initiated by hypercholesterolemia. Recently, the mouse has become the best model for experimental atherosclerosis. It was in 1992 that the first line of gene targeted mice, namely apolipoprotein E-knockout mice was developed. The apoE-deficient model develops extensive atherosclerotic lesions on a chow diet. The LDL receptor - deficient model has elevated LDL levels, but no lesions, or only very small lesions, form on the chow diet. However, robust lesions do form on the westerntype diet. The creation of apoE- knockout mice has changed the face of atherosclerosis research. Gene-targeted mouse models has changed the face of atherosclerotic research and helped in creation of the new theory of atherosclerosis: as an inflammatory disease. Recently, the mouse has become the best model for experimental atherosclerosis. It was in 1992 that the first line of gene targeted mice, namely apolipoprotein E-knockout mice was developed. The apoE-deficient model develops extensive atherosclerotic lesions on a chow diet. It is also the model in which the lesions have been characterized most thoroughly. The lesions develop into fibrous plaques; however, there is no evidence that plaque rupture occurs in this model. The LDL receptor - deficient model has elevated LDL levels, but no lesions, or only very small lesions, form on the chow diet. However, robust lesions do form on the western-type diet. The creation of apoE-knockout mice has changed the face of atherosclerosis research. Gene-targeted mouse models has changed the face of atherosclerotic research and helped in creation of the new theory of atherosclerosis: as an inflammatory disease. Nowadays, apoE- knockout mice model is therefore used in developing new drugs against atherosclerosis. This review describes how new groups of agents are searched.
虽然动脉粥样硬化以前被认为主要是一种退行性疾病，但现在已经确定其发病机制是炎症。载脂蛋白 E 敲除小鼠在理解动脉粥样硬化的炎症背景方面起着关键作用。目前，动脉粥样硬化被认为是一种慢性炎症性疾病，在大多数情况下是由高胆固醇血症引起的。最近，小鼠已成为实验性动脉粥样硬化的最佳模型。1992 年，首次开发了第一代基因靶向小鼠，即载脂蛋白 E 敲除小鼠。apoE 缺陷型模型在普通饮食中会发展出广泛的动脉粥样硬化病变。LDL 受体缺陷型模型的 LDL 水平升高，但在普通饮食中不会形成病变，或者仅形成非常小的病变。然而，在西方饮食类型下会形成坚固的病变。apoE 敲除小鼠的创建改变了动脉粥样硬化研究的面貌。基因靶向小鼠模型改变了动脉粥样硬化研究的面貌，并有助于形成动脉粥样硬化的新理论：作为一种炎症性疾病。最近，小鼠已成为实验性动脉粥样硬化的最佳模型。1992 年，首次开发了第一代基因靶向小鼠，即载脂蛋白 E 敲除小鼠。apoE 缺陷型模型在普通饮食中会发展出广泛的动脉粥样硬化病变。这也是病变特征最全面的模型。病变发展成纤维斑块；然而，在这个模型中没有证据表明斑块破裂发生。LDL 受体缺陷型模型的 LDL 水平升高，但在普通饮食中不会形成病变，或者仅形成非常小的病变。然而，在西方饮食类型下会形成坚固的病变。apoE 敲除小鼠的创建改变了动脉粥样硬化研究的面貌。基因靶向小鼠模型改变了动脉粥样硬化研究的面貌，并有助于形成动脉粥样硬化的新理论：作为一种炎症性疾病。如今，apoE 敲除小鼠模型被用于开发针对动脉粥样硬化的新药。本文综述了如何寻找新的药物。
