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

Atherosclerosis. 2009 Nov;207(1):1-7. doi: 10.1016/j.atherosclerosis.2009.03.024. Epub 2009 Apr 1.

Abstract

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.

Publication types

  • Biography
  • Historical Article
  • Portrait
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Biomedical Research / history*
  • Coronary Artery Disease / drug therapy
  • Coronary Artery Disease / genetics
  • Coronary Artery Disease / history*
  • Coronary Artery Disease / metabolism
  • Disease Models, Animal
  • Drug Evaluation, Preclinical / history
  • History, 20th Century
  • History, 21st Century
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / history
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Hyperlipidemias / complications
  • Hyperlipidemias / drug therapy
  • Hyperlipidemias / genetics
  • Hyperlipidemias / history*
  • Hyperlipidemias / metabolism
  • Lipoproteins / metabolism
  • Myocardial Infarction / genetics
  • Myocardial Infarction / history*
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / prevention & control
  • Rabbits
  • Receptors, LDL / deficiency
  • Receptors, LDL / genetics

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipoproteins
  • Receptors, LDL

Personal name as subject

  • Yoshio Watanabe