The History of the WHHL Rabbit, an Animal Model of Familial Hypercholesterolemia (II) - Contribution to the Development and Validation of the Therapeutics for Hypercholesterolemia and Atherosclerosis.

A number of effective drugs have been developed through animal experiments, contributing to the health of many patients. In particular, the WHHL rabbit family (WHHL rabbits and its advanced strains (coronary atherosclerosis-prone WHHL-CA rabbits and myocardial infarction-prone WHHLMI rabbits) developed at Kobe University (Kobe, Japan) contributed greatly in the development of cholesterol-lowering agents. The WHHL rabbit family is animal models for human familial hypercholesterolemia, coronary atherosclerosis, and coronary heart disease. At the end of breeding of the WHHL rabbit family, this review summarizes the contribution of the WHHL rabbit family to the development of lipid-lowering agents and anti-atherosclerosis agents. Studies using the WHHL rabbit family demonstrated, for the first time in the world, that lowering serum cholesterol levels or preventing LDL oxidation can suppress the progression and destabilization of coronary lesions. In addition, the WHHL rabbit family contributed to the development of various compounds that exhibit lipid-lowering and anti-atherosclerotic effects and has also been used in studies of gene therapeutics. Furthermore, this review also discusses the causes of the increased discrepancy in drug development between the results of animal experiments and clinical studies, which became a problem in recent years, and addresses the importance of the selection of appropriate animal models used in studies in addition to an appropriate study design.