Developing a novel rabbit model of atherosclerotic plaque rupture and thrombosis by cold-induced endothelial injury

28 healthy male New Zealand white rabbits were randomly divided into two groups: rabbits in group A (n = 12) were only fed a high-fat diet for eight weeks; rabbits in group B (n = 16) underwent cold-induced endothelial injury with liquid nitrogen, then were given a high-fat diet for eight weeks. After completion of the preparatory regimen, triggering of plaque rupture was attempted by local injection of liquid nitrogen in both groups.All rabbits in group B had disrupted plaques or rupture-driven occlusive thrombus formation, but none in group A showed any effects. More importantly, the cold-induced plaques in our model were reminiscent of human atherosclerotic plaques in terms of architecture, cellular composition, growth characteristics, and patterns of lipid accumulation.We successfully developed a novel rabbit model of atherosclerotic plaque rupture and thrombosis, which is simple, fast, inexpensive, and reproducible, and has a low mortality and a high yield of triggering. This model will allow us to better understand the mechanism of human plaque rupture and also to develop plaque-stabilizing therapies.It is now recognized that atherosclerotic plaque rupture and ensuing occlusive thrombus formation play an important role in the onset of two major causes of death in developed countries: acute coronary syndrome (ACS) and ischemic stroke[1,2]. By its very nature, plaque rupture is difficult to study directly in humans. A good animal model would help us to understand not only how plaque rupture and thrombus formation occur, but also how to take measures to prevent these from happening.Over the years, many animal models of atherosclerosis have been developed. In recent years, several models of plaque rupture and thrombosis have also begun to emerge. However, all of the existing models, such as balloon-induced and biological or mechanical triggering rabbit models [3-6], the Watanabe heritable hyperlipidemic (WHHL) rabbit model [7], and the apolipoprotein E (ApoE) or t