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Curr Opin Lipidol. 2008 Dec;19(6):631-6. doi: 10.1097/MOL.0b013e3283189c18.

Unstable coronary plaques and cardiac events in myocardial infarction-prone Watanabe heritable hyperlipidemic rabbits: questions and quandaries.

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Institute for Experimental Animals, Kobe University School of Medicine, Kobe, Hyogo, Japan.



Use of suitable animal models is essential for investigation of the mechanisms underlying cardiac events and development of the therapeutic strategies; however, ideal animal models that can recapitulate human coronary atherosclerosis and subsequent acute myocardial infarction are still lacking. In this article, we review the insights learned from myocardial infarction-prone Watanabe heritable hyperlipidemic (designated as WHHLMI) rabbits and discuss the possibility of using this model for the study of human acute coronary syndromes.


The vulnerable plaques of human coronary arteries are histologically characterized by a large lipid core and a thin fibrous cap with inflammatory cells. Recent studies have revealed that inflammatory cells and inflammatory mediators (such as cytokines and matrix metalloproteinases) play an important role in the plaque rupture.


We developed the WHHLMI rabbit that shows spontaneous myocardial infarction caused by coronary atherosclerosis. The coronary lesions of WHHLMI rabbits have features of fatty streaks, fibrous plaques, and fibroatheromatous plaques. Some plaques contain a lipid core and a thin fibrous cap similar to human vulnerable plaques. In spite of this, the plaque rupture is not observed in WHHLMI rabbits, suggesting that other additional factors such as mechanical stress are required to trigger the rupture. WHHLMI rabbits may become an important means for elucidating the possible mechanisms of plaque rupture by exposing the plaques to additional risk factors beyond hyperlipidemia.

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