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Development of Advanced Atherosclerotic Plaque by Injection of Inflammatory Proteins in a Rabbit Iliac Artery Model

 Jung-Sun Kim  ;  Seul-Gee Lee  ;  Jaewon Oh  ;  Sungha Park  ;  Se-Il Park  ;  Sung-Yu Hong  ;  Sehoon Kim  ;  Sang-Hak Lee  ;  Young-Guk Ko  ;  Donghoon Choi  ;  Myeong-Ki Hong  ;  Yangsoo Jang 
 YONSEI MEDICAL JOURNAL, Vol.57(5) : 1095-1105, 2016 
Journal Title
Issue Date
Rabbit model ; atherosclerosis ; balloon injury ; inflammatory protein
Animals ; Cholesterol, Dietary/administration & dosage ; Disease Models, Animal* ; Endothelium/surgery ; HMGB1 Protein/adverse effects* ; Iliac Artery/diagnostic imaging ; Iliac Artery/pathology ; Iliac Artery/surgery ; Injections, Intra-Arterial ; Macrophages ; Male ; Olive Oil/adverse effects ; Plaque, Atherosclerotic/chemically induced* ; Plaque, Atherosclerotic/diagnostic imaging ; Plaque, Atherosclerotic/pathology ; Rabbits ; Sodium Chloride/adverse effects ; Tomography, Optical Coherence ; Tumor Necrosis Factor-alpha/adverse effects*
PURPOSE: Appropriate animal models of atherosclerotic plaque are crucial to investigating the pathophysiology of atherosclerosis, as well as for the evaluation of the efficacy and safety of vascular devices. We aimed to develop a novel animal model that would be suitable for the study of advanced atherosclerotic lesions in vivo. MATERIALS AND METHODS: Atherosclerotic plaque was induced in 24 iliac arteries from 12 rabbits by combining a high cholesterol diet, endothelial denudation, and injection into the vessel wall with either saline (n=5), olive oil (n=6), or inflammatory proteins [n=13, high-mobility group protein B1 (HMGB1) n=8 and tumor necrosis factor (TNF)-α n=5] using a Cricket™ Micro-infusion catheter. Optical coherence tomography (OCT) was performed to detect plaque characteristics after 4 weeks, and all tissues were harvested for histological evaluation. RESULTS: Advanced plaque was more frequently observed in the group injected with inflammatory proteins. Macrophage infiltration was present to a higher degree in the HMGB1 and TNF-α groups, compared to the oil or saline group (82.1±5.1% and 94.6±2.2% compared to 49.6±14.0% and 46.5±9.6%, p-value<0.001), using RAM11 antibody staining. On OCT, lipid rich plaques were more frequently detected in the inflammatory protein group [saline group: 2/5 (40%), oil group: 3/5 (50%), HMGB1 group: 6/8 (75%), and TNF-α group: 5/5 (100%)]. CONCLUSION: These data indicate that this rabbit model of atherosclerotic lesion formation via direct injection of pro-inflammatory proteins into the vessel wall is useful for in vivo studies investigating atherosclerosis.
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Ko, Young Guk(고영국) ORCID logo https://orcid.org/0000-0001-7748-5788
Kim, Se Hoon(김세훈) ORCID logo https://orcid.org/0000-0001-7516-7372
Kim, Jung Sun(김중선) ORCID logo https://orcid.org/0000-0003-2263-3274
Park, Sung Ha(박성하) ORCID logo https://orcid.org/0000-0001-5362-478X
Oh, Jae Won(오재원) ORCID logo https://orcid.org/0000-0002-4585-1488
Lee, Sang Hak(이상학) ORCID logo https://orcid.org/0000-0002-4535-3745
Jang, Yang Soo(장양수) ORCID logo https://orcid.org/0000-0002-2169-3112
Choi, Dong Hoon(최동훈) ORCID logo https://orcid.org/0000-0002-2009-9760
Hong, Myeong Ki(홍명기) ORCID logo https://orcid.org/0000-0002-2090-2031
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