The Watanabe heritable hyperlipidemic (WHHL) rabbit, its characteristics and history of development: A tribute to the late Dr. Yoshio Watanabe

Professor Yoshio Watanabe, who developed the WHHL rabbit, died on December 13, 2008. He had contributed to studies of lipoprotein metabolism and atherosclerosis, and to the development of hypolipidemic and/or anti-atherosclerotic compounds. WHHL rabbits show hypercholesterolemia due to deficiency of LDL receptors, and very similar lipoprotein metabolism to humans. The incidences of coronary atherosclerosis and myocardial infarction in the original WHHL rabbits were very low. After three rounds of selective breeding, the coronary plaques changed to fibroatheromas with thin fibrous caps and myocardial infarction developed spontaneously. In studies with WHHL rabbits, plaque-stabilizing effects of statins were proved. In this review, we admire his achievements and describe the history of studies using WHHL rabbits.