A Novel Rabbit Model Of Unstable Atherosclerotic Plaque: Developed By Dehydrated Ethanol-induced Endothelial Injury And High Cholesterol Diet

Background and Objective: The cardiovascular disease caused by atherosclerosis has become the mostimportant killer of human health, according to WHO each year nearly over seventeen million people died of acutecardiovascular events. Rupture of the unstable atherosclerotic plaque is the major cause of morbidity and mortalityof atherosclerosis in human. Because the lacking of suitable animal model, the research results about itspathogenesis and treatment strategy are very limited. We sought to develop a novel animal model of unstable evenrupture atherosclerotic plaque to be a tool for the new therapeutic target and diagnostic techniques.Methods: Forty adult male New Zealand white rabbits were randomly assigned to two groups: controlgroup (n=10), in which normal rabbits were fed a standard chow diet for12weeks, and experimental group(n=30), in which normal rabbits received a western-type diet for12weeks. Rabbits in the experimental groupwere divided randomly into three groups: simple high-fat diet group(n=10), ethanol injuried10seconds(n=10) and15seconds group(n=10). At the end of12th week, the right common carotid artery was harvested forhistopathologic examination, and the Image Analysis Software (Image-ProPlus5.0) was used to measure thevascular intima and media thickness and the proportion of various cellular components in the vascular wall. At thesame time, the serum lipid levels were assayed. In addition,320CT angiography was performed on the rabbitcarotid artery to confirm the lesion.Results: Control group and simple high-fat diet group did not showed obvious atherosclerotic plaqueformation, the maximum of intimal thickness(9.95±1.3μm；10.74±1.08μm) and the maximal mediathickness(64.71±5.49μm；72.43±3.6μm) were no significant difference between this two groups. The10s groupand the15s group formed a typical atherosclerotic plaque, the maximum of intimal thickness(396.46±70.08μm；613±110.69μm) and the maximal media thickness(139.4±24.4μm；142.84±15.77μm) were obvious thickeningcompared with the former two groups. There were more macrophages and matrix metalloproteinases9, lesssmooth muscle cells in the atherosclerotic plaques in15s group compared with10s group. The result of serumlipid testing showed that the total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP) were significantly increased afterhigh-fat diet feeding. The320CT angiography was performed on the rabbit occurred clinical events, the resultsindicated that the stenosis degree of right common carotid artery was90%, and the distal embolia was found at themiddle cerebral artery.Conclusion: We developed a unique rabbit model of unstable atherosclerotic plaque by using thedehydrated ethanol and combining with the high cholesterol diet. Because the model has the advantages of simpleoperation, high repeatability, short time-consuming, low animal mortality, it is expected to be widely recognizedby the public. Meanwhile it would be a good tool for the researches of disease diagnosis, prevention, treatmentand so on.