A minimally invasive animal model of atherosclerosis and neointimal hyperplasia for translational research

Abstract Background A variety of animal models has been developed for research on atherosclerosis and neointimal hyperplasia. While small animal models contain limits for translational research, we aimed to develop an atherosclerosis model with lumen-narrowing plaques to foster basic research in vas...

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Main Authors: Max L. A. Ebert, Vanessa F. Schmidt, Osman Öcal, Anne von Thaden, Olaf Dietrich, Bastian Popper, Sandra Elges, Max Seidensticker, Jens Ricke, Melanie A. Kimm, Astrid Jeibmann, Moritz Wildgruber
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Language:English
Published: SpringerOpen 2025-02-01
Series:European Radiology Experimental
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Online Access:https://doi.org/10.1186/s41747-025-00558-1
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author Max L. A. Ebert
Vanessa F. Schmidt
Osman Öcal
Anne von Thaden
Olaf Dietrich
Bastian Popper
Sandra Elges
Max Seidensticker
Jens Ricke
Melanie A. Kimm
Astrid Jeibmann
Moritz Wildgruber
author_facet Max L. A. Ebert
Vanessa F. Schmidt
Osman Öcal
Anne von Thaden
Olaf Dietrich
Bastian Popper
Sandra Elges
Max Seidensticker
Jens Ricke
Melanie A. Kimm
Astrid Jeibmann
Moritz Wildgruber
author_sort Max L. A. Ebert
collection DOAJ
description Abstract Background A variety of animal models has been developed for research on atherosclerosis and neointimal hyperplasia. While small animal models contain limits for translational research, we aimed to develop an atherosclerosis model with lumen-narrowing plaques to foster basic research in vascular biology, the development of new angioplasty devices, and vessel wall imaging approaches. Methods Endothelial denudation was performed via a minimally invasive approach through the auricular artery, followed by stent-retriever mediated endothelial injury in New Zealand White rabbits (n = 10). Along with a high-fat diet, the rabbits developed lumen-narrowing atherosclerosis and neointimal hyperplasia of the iliac arteries within a 6-week period after mechanical injury. The stent-retriever method was compared with a conventional rabbit model (n = 10) using balloon denudation via surgical access, and both models were analyzed with a particular focus on animal welfare. Fisher’s exact, Mann–Whitney U, and unpaired t-tests were used. Results The average time for the entire procedure was 62 min for the balloon group and 31 min for the stent-retriever group (p < 0.001). The stent-retriever model resulted in less periprocedural morbidity (including expenditure, intubation time, anesthetics, and end-tidal CO2 level) and mortality (40% mortality in the conventional group compared to 0% in the stent-retriever model, p = 0.011), while generating lumen-narrowing atherosclerotic lesions with key features as compared to humans as revealed by time-of-flight magnetic resonance imaging and histology. Conclusion We developed a minimally invasive model of iliac atherosclerosis with high reproducibility and improved animal welfare for translational research. Relevance statement This advanced rabbit model could allow for translational research in atherosclerosis, including pharmacological investigations as well as research on interventional angioplasty procedures. Key Points Rabbit models show similar lipid metabolism as humans. Stent-retriever mediated endothelial denudation causes neointimal hyperplasia and lumen narrowing. This minimal invasive model allows for clinical translation, including pharmacological investigations and vessel wall imaging. Graphical Abstract
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spelling doaj-art-e6c53ea2ed4b46abadd8eaad1eda3fd02025-02-09T12:11:21ZengSpringerOpenEuropean Radiology Experimental2509-92802025-02-019111110.1186/s41747-025-00558-1A minimally invasive animal model of atherosclerosis and neointimal hyperplasia for translational researchMax L. A. Ebert0Vanessa F. Schmidt1Osman Öcal2Anne von Thaden3Olaf Dietrich4Bastian Popper5Sandra Elges6Max Seidensticker7Jens Ricke8Melanie A. Kimm9Astrid Jeibmann10Moritz Wildgruber11Department of Radiology, University Hospital, LMU MunichDepartment of Radiology, University Hospital, LMU MunichDepartment of Radiology, University Hospital, LMU MunichVeterinary PracticeDepartment of Radiology, University Hospital, LMU MunichBiomedical Center, Core Facility Animal Models, Faculty of Medicine, Ludwig-Maximilians-Universität MünchenGerhard-Domagk-Institute of Pathology, Münster University HospitalDepartment of Radiology, University Hospital, LMU MunichDepartment of Radiology, University Hospital, LMU MunichDepartment of Radiology, University Hospital, LMU MunichInstitute of Neuropathology, University Hospital MünsterDepartment of Radiology, University Hospital, LMU MunichAbstract Background A variety of animal models has been developed for research on atherosclerosis and neointimal hyperplasia. While small animal models contain limits for translational research, we aimed to develop an atherosclerosis model with lumen-narrowing plaques to foster basic research in vascular biology, the development of new angioplasty devices, and vessel wall imaging approaches. Methods Endothelial denudation was performed via a minimally invasive approach through the auricular artery, followed by stent-retriever mediated endothelial injury in New Zealand White rabbits (n = 10). Along with a high-fat diet, the rabbits developed lumen-narrowing atherosclerosis and neointimal hyperplasia of the iliac arteries within a 6-week period after mechanical injury. The stent-retriever method was compared with a conventional rabbit model (n = 10) using balloon denudation via surgical access, and both models were analyzed with a particular focus on animal welfare. Fisher’s exact, Mann–Whitney U, and unpaired t-tests were used. Results The average time for the entire procedure was 62 min for the balloon group and 31 min for the stent-retriever group (p < 0.001). The stent-retriever model resulted in less periprocedural morbidity (including expenditure, intubation time, anesthetics, and end-tidal CO2 level) and mortality (40% mortality in the conventional group compared to 0% in the stent-retriever model, p = 0.011), while generating lumen-narrowing atherosclerotic lesions with key features as compared to humans as revealed by time-of-flight magnetic resonance imaging and histology. Conclusion We developed a minimally invasive model of iliac atherosclerosis with high reproducibility and improved animal welfare for translational research. Relevance statement This advanced rabbit model could allow for translational research in atherosclerosis, including pharmacological investigations as well as research on interventional angioplasty procedures. Key Points Rabbit models show similar lipid metabolism as humans. Stent-retriever mediated endothelial denudation causes neointimal hyperplasia and lumen narrowing. This minimal invasive model allows for clinical translation, including pharmacological investigations and vessel wall imaging. Graphical Abstracthttps://doi.org/10.1186/s41747-025-00558-1Endothelium (vascular)Models (animals)NeointimaPlaque (atherosclerotic)Stents
spellingShingle Max L. A. Ebert
Vanessa F. Schmidt
Osman Öcal
Anne von Thaden
Olaf Dietrich
Bastian Popper
Sandra Elges
Max Seidensticker
Jens Ricke
Melanie A. Kimm
Astrid Jeibmann
Moritz Wildgruber
A minimally invasive animal model of atherosclerosis and neointimal hyperplasia for translational research
European Radiology Experimental
Endothelium (vascular)
Models (animals)
Neointima
Plaque (atherosclerotic)
Stents
title A minimally invasive animal model of atherosclerosis and neointimal hyperplasia for translational research
title_full A minimally invasive animal model of atherosclerosis and neointimal hyperplasia for translational research
title_fullStr A minimally invasive animal model of atherosclerosis and neointimal hyperplasia for translational research
title_full_unstemmed A minimally invasive animal model of atherosclerosis and neointimal hyperplasia for translational research
title_short A minimally invasive animal model of atherosclerosis and neointimal hyperplasia for translational research
title_sort minimally invasive animal model of atherosclerosis and neointimal hyperplasia for translational research
topic Endothelium (vascular)
Models (animals)
Neointima
Plaque (atherosclerotic)
Stents
url https://doi.org/10.1186/s41747-025-00558-1
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