Bocan T M
Department of Vascular and Cardiac Diseases, Parke-Davis Pharmaceutical Research, Division of Warner Lambert Company, Ann Arbor, MI 48105, USA.
Curr Pharm Des. 1998 Feb;4(1):37-52.
Atherosclerosis has often been defined as a multifactoral disease; however, a common risk factor associated with accelerated vascular disease in man or animals is an elevated plasma cholesterol level. Even though there is no one perfect animal model that completely replicates the stages of human atherosclerosis, cholesterol feeding and mechanical endothelial injury are two common features shared by most models of atherosclerosis. The models may differ with respect to degree of dietary cholesterol supplementation, length of hypercholesterolemia, dietary regimen and type, duration and degree of mechanical endothelial injury. With the advent of genetic engineering, transgenic mouse models have supplemented the classical dietary cholesterol induced disease models such as the cholesterol-fed hamster, rabbit, pig and monkey. The desire to limit the progression of atherosclerosis has spawned numerous drug intervention studies. Biochemical as well as morphologic and morphometric changes in the extent, structure and composition of atherosclerotic lesions following drug intervention have become major endpoints of in vivo drug intervention studies. Interpretations of alterations in vascular pathology following drug administration are often confounded by associated changes in plasma lipids and lipoproteins, limitation of the animal models and additional properties of compounds unrelated to their primary mode of action. Thus, the current review will summarize the pathology of atherosclerosis, describe various animal models of vascular disease and provide a critical review of the methods utilized and conclusions drawn when evaluating pharmacologic agents in animals.
动脉粥样硬化常被定义为一种多因素疾病；然而，在人类或动物中，与血管疾病加速相关的一个常见风险因素是血浆胆固醇水平升高。尽管没有一种完美的动物模型能完全复制人类动脉粥样硬化的各个阶段，但喂食胆固醇和机械性内皮损伤是大多数动脉粥样硬化模型共有的两个常见特征。这些模型在饮食中胆固醇补充的程度、高胆固醇血症的持续时间、饮食方案和类型、机械性内皮损伤的持续时间和程度等方面可能存在差异。随着基因工程的出现，转基因小鼠模型补充了经典的饮食胆固醇诱导疾病模型，如喂食胆固醇的仓鼠、兔子、猪和猴子。限制动脉粥样硬化进展的需求催生了大量药物干预研究。药物干预后动脉粥样硬化病变的范围、结构和组成的生化以及形态学和形态计量学变化已成为体内药物干预研究的主要终点。药物给药后血管病理学改变的解读常常因血浆脂质和脂蛋白的相关变化、动物模型的局限性以及与化合物主要作用方式无关的其他特性而变得复杂。因此，本综述将总结动脉粥样硬化的病理学，描述各种血管疾病动物模型，并对在动物中评估药物制剂时所采用的方法和得出的结论进行批判性综述。
