title: Development of Advanced Atherosclerotic Plaque by Injection of Inflammatory Proteins in a Rabbit Iliac Artery Model.
abstract: OBJECTIVE
  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.
  
  
  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%)].
  
  
  CONCLUSIONS
  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.
authors.affiliation: Cardiology Division, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Korea.|Cardiovascular Product Evaluation Center, Yonsei University College of Medicine, Seoul, Korea.|Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jung Sun
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Graduate Program in Science for Aging, Yonsei University, Seoul, Korea.
authors.forename: Seul Gee
authors.initials: SG
authors.lastname: Lee
authors.affiliation: Cardiology Division, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Korea.|Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jaewon
authors.initials: J
authors.lastname: Oh
authors.affiliation: Cardiology Division, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Korea.|Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, Korea. shpark0530@yuhs.ac.
authors.forename: Sungha
authors.initials: S
authors.lastname: Park
authors.affiliation: Cardiovascular Product Evaluation Center, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Se Il
authors.initials: SI
authors.lastname: Park
authors.affiliation: Cardiovascular Product Evaluation Center, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Sung Yu
authors.initials: SY
authors.lastname: Hong
authors.affiliation: Department of Pathology, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Sehoon
authors.initials: S
authors.lastname: Kim
authors.affiliation: Cardiology Division, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Korea.|Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Sang Hak
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Cardiology Division, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Korea.|Cardiovascular Product Evaluation Center, Yonsei University College of Medicine, Seoul, Korea.|Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Young Guk
authors.initials: YG
authors.lastname: Ko
authors.affiliation: Cardiology Division, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Korea.|Cardiovascular Product Evaluation Center, Yonsei University College of Medicine, Seoul, Korea.|Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Donghoon
authors.initials: D
authors.lastname: Choi
authors.affiliation: Cardiology Division, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Korea.|Cardiovascular Product Evaluation Center, Yonsei University College of Medicine, Seoul, Korea.|Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, Korea.|Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Myeong Ki
authors.initials: MK
authors.lastname: Hong
authors.affiliation: Cardiology Division, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul, Korea.|Cardiovascular Product Evaluation Center, Yonsei University College of Medicine, Seoul, Korea.|Cardiovascular Research Institute, Yonsei University College of Medicine, Seoul, Korea.|Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Yangsoo
authors.initials: Y
authors.lastname: Jang
mesh_terms: D000818:Animals; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D004195:Disease Models, Animal; D004727:Endothelium / Q000601:surgery; D024243:HMGB1 Protein / Q000009:adverse effects*; D007083:Iliac Artery / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery; D007269:Injections, Intra-Arterial; D008264:Macrophages; D008297:Male; D000069463:Olive Oil / Q000009:adverse effects; D058226:Plaque, Atherosclerotic / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000473:pathology; D011817:Rabbits; D012965:Sodium Chloride / Q000009:adverse effects; D041623:Tomography, Optical Coherence; D014409:Tumor Necrosis Factor-alpha / Q000009:adverse effects*
chemical_list: D002791:Cholesterol, Dietary; D024243:HMGB1 Protein; D000069463:Olive Oil; D014409:Tumor Necrosis Factor-alpha; D012965:Sodium Chloride
keywords: Rabbit model; atherosclerosis; balloon injury; inflammatory protein