Kobayashi Tsutomu, Ito Takashi, Shiomi Masashi
Institute for Experimental Animals, Kobe University Graduate School of Medicine, Chuo-ku, Kobe, Japan.
J Biomed Biotechnol. 2011;2011:406473. doi: 10.1155/2011/406473. Epub 2011 Apr 19.
Conquering cardiovascular diseases is one of the most important problems in human health. To overcome cardiovascular diseases, animal models have played important roles. Although the prevalence of genetically modified animals, particularly mice and rats, has contributed greatly to biomedical research, not all human diseases can be investigated in this way. In the study of cardiovascular diseases, mice and rats are inappropriate because of marked differences in lipoprotein metabolism, pathophysiological findings of atherosclerosis, and cardiac function. On the other hand, since lipoprotein metabolism and atherosclerotic lesions in rabbits closely resemble those in humans, several useful animal models for these diseases have been developed in rabbits. One of the most famous of these is the Watanabe heritable hyperlipidemic (WHHL) rabbit, which develops hypercholesterolemia and atherosclerosis spontaneously due to genetic and functional deficiencies of the low-density lipoprotein (LDL) receptor. The WHHL rabbit has been improved to develop myocardial infarction, and the new strain was designated the myocardial infarction-prone WHHL (WHHLMI) rabbit. This review summarizes the importance of selecting animal species for translational research in biomedical science, the development of WHHL and WHHLMI rabbits, their application to the development of hypocholesterolemic and/or antiatherosclerotic drugs, and future prospects regarding WHHL and WHHLMI rabbits.
攻克心血管疾病是人类健康领域最重要的问题之一。为了战胜心血管疾病，动物模型发挥了重要作用。尽管转基因动物，尤其是小鼠和大鼠的广泛应用极大地推动了生物医学研究，但并非所有人类疾病都能通过这种方式进行研究。在心血管疾病的研究中，小鼠和大鼠并不适用，因为它们在脂蛋白代谢、动脉粥样硬化的病理生理表现以及心脏功能方面存在显著差异。另一方面，由于兔子的脂蛋白代谢和动脉粥样硬化病变与人类非常相似，因此已经开发出了几种针对这些疾病的有用动物模型。其中最著名的是渡边遗传性高脂血症（WHHL）兔，它由于低密度脂蛋白（LDL）受体的遗传和功能缺陷而自发地发展为高胆固醇血症和动脉粥样硬化。WHHL兔已经经过改良以诱发心肌梗死，新的品系被命名为易患心肌梗死的WHHL（WHHLMI）兔。本综述总结了在生物医学科学转化研究中选择动物物种的重要性、WHHL和WHHLMI兔的培育、它们在降胆固醇和/或抗动脉粥样硬化药物研发中的应用以及关于WHHL和WHHLMI兔的未来前景。
