It is generally considered that coronary
rupture-prone plaques play an important role in the onset of sudden
cardiac events (
acute coronary syndromes/
sudden cardiac death). However, it is not clear which factors or stimuli are required to trigger plaque
rupture and whether coronary plaques without occlusive thrombi can cause sudden
cardiac events. To address these issues, recently, we developed a rabbit model of spontaneous
myocardial infarction [the Watanabe heritable hyperlipidemic (WHHL) MI rabbit] and found that this model possessed several types of coronary plaques that are possibly correlated to sudden
cardiac events. Although many of the coronary plaques of the WHHLMI rabbits appeared histologically to be
rupture-prone in nature, true
rupture was detected only in the few animals that died of MI. In addition, no occlusive
thrombus was detected in any WHHLMI rabbit. These findings suggest that some additional stimuli play a definitive role in causing disruption of
rupture-prone plaques and
thrombosis. Nearly-occluded plaques caused by a
luminal macrophage accumulation are the most common feature of WHHLMI rabbits, suggesting that they are responsible for sudden
cardiac events. The WHHLMI rabbit could be a useful model for studying the mechanism(s) of plaque
rupture and thrombogenesis if plaque
rupture/
thrombus formation is induced in the
rupture-prone plaques of WHHLMI rabbits by administration of additional triggering factors, and could provide a novel means for developing new
therapies.