PMID- 35070793 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220430 IS - 2223-3652 (Print) IS - 2223-3660 (Electronic) IS - 2223-3652 (Linking) VI - 11 IP - 6 DP - 2021 Dec TI - A novel animal model for vulnerable atherosclerotic plaque: dehydrated ethanol lavage in the carotid artery of rabbits fed a Western diet. PG - 1241-1252 LID - 10.21037/cdt-21-291 [doi] AB - BACKGROUND: The study of unstable atherosclerotic plaques is limited by the absence of ideal animal models to reproduce the plaque instability observed in humans. In this study, we attempted to develop a novel animal model for vulnerable atherosclerotic plaques using dehydrated ethanol lavage in rabbits fed a Western diet (WD). METHODS: A total of 30 New Zealand White (NZW) rabbits were randomized to 5 groups, including a control group with or without WD, a balloon injury with WD group, and an ethanol injury with or without WD group. Operations were conducted using the right common carotid artery as the target vessel. All animals were followed up for 3 months unless a vascular event occurred. Blood samples and carotid artery specimens were ultimately collected for analysis of atherogenesis. RESULTS: Compared to rabbits in which lesions were induced by balloon injury, those subjected to an ethanol lavage with high cholesterol diet showed progressive atherosclerotic lesions in all carotid artery segments, which were characterized by greater plaque burden, smaller minimum lumen area (MLA), and increased vulnerability as indicated by abundant macrophages, scattered smooth muscle cell (SMC) composition, higher matrix metalloproteinase-9 (MMP-9) expression in plaques, thinner fibrous cap thickness, and higher possibility of stroke event (50% vs. 0%). Meanwhile, the serum interleukin-1beta (IL-1beta) and monocyte chemoattractant protein-1 (MCP-1) levels in the ethanol injury group with a high-cholesterol diet were significantly higher than those in the balloon injury group after 3 months (all P<0.01). CONCLUSIONS: We successfully established a novel animal model for vulnerable atherosclerosis by ethanol exposure of the carotid segment that has a higher predictive value for the probability of ischemic events than the balloon injury model. Therefore, it may represent a promising animal model for investigating new therapeutic approaches, novel imaging modalities, and underlying mechanisms for vulnerable atherosclerotic plaque. CI - 2021 Cardiovascular Diagnosis and Therapy. All rights reserved. FAU - Zhao, Ruochi AU - Zhao R AD - Cardiology Center, Ningbo First Hospital, Ningbo University, Ningbo, China. FAU - Liu, Hongyan AU - Liu H AD - Neurology Department, Ningbo First Hospital, Ningbo University, Ningbo, China. FAU - Zhang, Shangshi AU - Zhang S AD - Cardiovascular Department, Shangrao People's Hospital, Shangrao, China. FAU - Lu, Qi AU - Lu Q AD - Cardiovascular Department, Yinzhou People's Hospital, Ningbo University, Ningbo, China. FAU - Fei, Xiaohong AU - Fei X AD - Cardiology Center, Ningbo First Hospital, Ningbo University, Ningbo, China. FAU - Zhou, Honglin AU - Zhou H AD - Cardiology Center, Ningbo First Hospital, Ningbo University, Ningbo, China. FAU - Liu, Junsong AU - Liu J AD - Cardiology Center, Ningbo First Hospital, Ningbo University, Ningbo, China. FAU - Ye, Honghua AU - Ye H AD - Cardiology Center, Ningbo First Hospital, Ningbo University, Ningbo, China. FAU - Chen, Xiaomin AU - Chen X AD - Cardiology Center, Ningbo First Hospital, Ningbo University, Ningbo, China. FAU - Cui, Hanbin AU - Cui H AD - Cardiology Center, Ningbo First Hospital, Ningbo University, Ningbo, China. LA - eng PT - Journal Article PL - China TA - Cardiovasc Diagn Ther JT - Cardiovascular diagnosis and therapy JID - 101601613 PMC - PMC8748485 OTO - NOTNLM OT - Animal model OT - endothelial cell (EC) injury OT - inflammatory marker OT - vulnerable atherosclerotic plaque COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/cdt-21-291). HC reports that the study was supported by grant of Zhejiang Provincial Natural Science Foundation, China (grant No. LY12H02001) and Zhejiang Provincial Key Research Project (grant No. 2021C03096). HY reports that the study was partly supported by Ningbo Social Development Research Project (Grant No. 2011C51003 to HY). The other authors have no conflicts of interest to declare. EDAT- 2022/01/25 06:00 MHDA- 2022/01/25 06:01 PMCR- 2021/12/01 CRDT- 2022/01/24 08:53 PHST- 2021/05/06 00:00 [received] PHST- 2021/10/25 00:00 [accepted] PHST- 2022/01/24 08:53 [entrez] PHST- 2022/01/25 06:00 [pubmed] PHST- 2022/01/25 06:01 [medline] PHST- 2021/12/01 00:00 [pmc-release] AID - cdt-11-06-1241 [pii] AID - 10.21037/cdt-21-291 [doi] PST - ppublish SO - Cardiovasc Diagn Ther. 2021 Dec;11(6):1241-1252. doi: 10.21037/cdt-21-291.