| BACKGROUND: (1) All preceding experimental studies of carotidendarterectomy (CEA) were carried out in normal arteries of healthyanimals, a basic pathological status, atherosclerosis, was ignored,then the reference significance of these experimental results forclinical work was limited considerably. It is an urgent need todevelop an animal model of carotid atherosclerotic stenosis (CASS)to meet the needs of associated experimental studies. (2) It isconfronted with great challenge to prevent or treat restenosis afterCEA clinically. Vascular endothelial growth factor (VEGF) is anendothelial cell-specific mitogen. It was reported recently that localdelivery of protein or gene of VEGF accelerated reendothelializationand attenuated intimal hyperplasia in balloon-injured rat carotidartery. But there was no any clinical or experimental report aboutapplying VEGF in the operation of CEA to prevent restenosis, andstill there was no report of the characteristics of VEGF expression inlocal artery wall pre- or post-CEA.PURPOSE: (1) To establish the methods and factors affecting thedevelopment of an economical, practical, stable and reliable animalmodel suitable for experimental studies of surgical treatments ofCASS. (2) To study the characteristics of VEGF and its geneexpression in CASS rabbit carotid arteries pre- and post-CEA, and toprovide scientific basis for experimental studying of VEGFpreventing restenosis after CEA.METHODS: (1) Using New Zealand Rabbits, lesions were created byair-drying an isolated segment of common carotid artery(120ml/min×15min) and feeding the rabbits a diet of 2% cholesterol,6% peanut oil for 15 days, 1 month, 2 months and 3 monthsseparately. Digital Subtraction Angiography was used to evaluatethe stenosis of carotid arteries. Many histological methods, such ashematoxylin-eosin staining, special staining and several kinds ofimmunohistochemicaI anaIyses, were used to illustrate thecharacteristics of the atherosclerotic Iesions, and then to screen outthe best method to deveIop the CASS animaI model. (2) CASS rabbitmodel were developed by the method of air-- drying carotid arteryand feeding the animal with a diet rich in fat as described in part (1 ).CEAs, imitating cIinical operations, were carried out in CASS rabbits.The arteries were fixed by intraarterial per fusion of fOrmaIin atphysiological pressure and then they were resected en bloc andimmersed in fOrmalin before CEA, immediately after CEA, 3 days, 7days and 21 days after CEA, separateIy. ImmunohistochemicaIanaIysis and in situ hybridization were used to study thecharacteristics of VEGF and its gene expression in CASS rabbitcarotid arteries pre- and post-CEA.RESULTS; (1 ) The average rates of stenosis were calcuIated anddescribed as foIIowing, half month group' 46.32% i 19.22%l 1-month groupt 72.80% i 19,28%; 2-month group: 73.47% l 22.26%;3-month group; 59.19% t 25.22%. The rates of moderate and severestenoses of aIl 4 groups were more than 80%, and the rates ofsevere stenoses of the last 3 groups (1 -month, 2-month and 3-monthgroup) were close to or more than 50%. The pathologicaI studiessuggested that the atheroscIerotic Iesions were getting more andmore serious as the feeding time went on. Fed the atherogenic dietfor 15 days, the Iesions feII into the fatty streak period ofatherosceIerosis; fed for 1 month, the Iesions were beIong to theearIy fibrous pIaque period; fed for 2 month, the Iesions felI into themature fibrous plaque period; and fed for 3 month, the Iesions werebeIong to the earIy atheromatous pIaque period, but were not in5conformity with the typicaI atheromatous plaque period. (2) OVEGF expression was not cIearly found in the intima and media ofnormal artery. @ But VEGF expression was strong inatherosclerotic arteries, mainIy Iocated in extracelluIar matrix. Highexpression of VEGF at the mRNA IeveI was also documented infoam ceIIs in atherosclero...
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