Abstract
Several animal models have been developed to study atherosclerosis. Here we present a rabbit atherosclerosis model generated by surgical denudation of the aortic endothelium in combination with a high-fat and cholesterol-enriched diet. This model is characterized by the formation of vascular lesions that exhibit several hallmarks of human atherosclerosis. Due to the rabbit’s relative large size, as compared to rodents, this model is suited for the imaging-guided evaluation of novel therapeutic strategies using clinical scanners. In this chapter, we present an extensive outline of the procedures to induce aortic atherosclerotic lesions in rabbits as well as methods to evaluate the disease, including noninvasive in vivo multiparametric imaging and histopathology.
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Acknowledgments
We would like to thank all the members of the large animal unit of the Center for Comparative Medicine and Surgery at the Icahn School of Medicine at Mount Sinai for their continual excellent technical support with this model. We also would like to thank René-Paul Lafarie for the great pictures of the angioplasty procedure. Histology images presented here were performed at the Microscopy Core at Icahn School of Medicine at Mount Sinai. PET/MR imaging was performed at the TMII Imaging Core at Icahn School of Medicine at Mount Sinai.
All experiments presented in this chapter were performed in accordance with protocols approved by the Radiation Safety Committee and the Institutional Animal Care and Use Committee of the Icahn School of Medicine at Mount Sinai and followed National Institutes of Health guidelines for animal welfare. Some of the artworks present in Fig. 1 are adapted from Servier Medical Art and used under a Creative Commons Attribution 3.0 Unported License.
Funding
This research was supported by “De Drie Lichten” Foundation in The Netherlands (M.L.S.), the American Heart Association 17PRE33660729 (M.L.S.), the National Heart, Lung, and Blood Institute (NHLBI), and the National Institutes of Health (NIH), as a Program of Excellence in Nanotechnology (PEN) Award, Contract #HHSN268201000045C, NIH/NIBIB R01 EB009638 (Z.A.F.), Harold S. Geneen Charitable Trust Award (Z.A.F.), R01 HL125703 (W.J.M.M.), NWO Vidi 91713324 (W.J.M.M.), and PSC-CUNY (F.F).
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Senders, M.L. et al. (2018). Development and Multiparametric Evaluation of Experimental Atherosclerosis in Rabbits. In: Ishikawa, K. (eds) Experimental Models of Cardiovascular Diseases. Methods in Molecular Biology, vol 1816. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8597-5_30
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DOI: https://doi.org/10.1007/978-1-4939-8597-5_30
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