Development of a Novel Murine Model of In-Stent Neoatherosclerosis
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(Published version)
Date
2025
Authors
Liu, J.
Geremew, D.
Sandeman, L.Y.
Nankivell, V.A.
Chen, R.
Xiang, L.
Solly, E.L.
Stretton, L.G.
Escarbe, S.
Blake, S.J.
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Journal article
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Journal of the American Heart Association, 2025; 14(22):e041260-1-e041260-16
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Jiandi Liu, Demeke Geremew, Lauren Y. Sandeman, Victoria A. Nankivell, Rouyan Chen, Lei Xiang, Emma L. Solly, Liam G. Stretton, Samantha Escarbe, Stephen J. Blake, Robert A. McLaughlin, Joanne T. M. Tan, Peter J. Psaltis, Claudine S. Bonder, Jiawen Li, Yanqing Wu, Christina A. Bursill
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Abstract
BACKGROUND: In-stent neoatherosclerosis is a complication of percutaneous coronary intervention with stenting. Although similar to de novo atherosclerosis, it develops rapidly within 1 to 5 years rather than over a lifetime. No preclinical small animal model exists to fully elucidate neoatherosclerosis biology or evaluate targeted therapies. This study aimed to establish and validate a novel murine model of in-stent neoatherosclerosis. METHODS: Murine stainless-steel stents (2.5×0.7 mm) were deployed into donor descending aortas of atherosclerosis-prone (Apo)e−/− (apolipoprotein E) mice, then carotid-interposition grafted into Apoe−/− recipients. Mice (n=6–8/group) received chow or a high-cholesterol diet for 7 or 28 days post surgery. A novel miniaturized probe was used to image the stented vessel of a mouse fed high-cholesterol diet for 28 days. Neointimas in stented vessels were histologically and flow cytometrically assessed. RESULTS: Bimodal intravascular imaging combined optical coherence tomography (plaque burden) with fluorescence detection of indocyanine green (plaque instability) to visualize in-stent neoatherosclerosis along the entire stented segment. Histological analyses revealed that stented vessels from mice fed high-cholesterol diet had neointimas with prominent lipid cores and abundant CD68+ macrophages, reminiscent of human neoatherosclerosis. Mice fed chow post stenting had distinctly different neointimas that were smooth muscle cell rich, resembling neointimal hyperplasia. Flow cytometry revealed a higher content of monocytes/macrophages in stented aortas from mice fed high-cholesterol diet than in nonstented aortas. CONCLUSIONS: We have developed and validated the first murine model that replicates the unique characteristics of human in-stent neoatherosclerosis. This has implications for exploring the mechanisms that promote neoatherosclerosis and testing targeted new therapies.
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© 2025 The Author(s). Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial- NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.