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TRP Channels in Drug Discovery pp 75–90Cite as

Atherosclerosis Models with Cell-Mediated Calcification

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Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

Abstract

This protocol describes a novel chronic total occlusion (CTO) model that features cell-mediated calcium deposits in rabbit femoral arteries. CTO is the most severe case of atherosclerosis, and it remains a big challenge in cardiology. There are urgent needs to establish a CTO animal model in order to develop new devices and drugs. The purpose of this protocol is to provide such a platform for advancing the treatment of CTOs.

Our CTO model features the following four prominent characteristics of a clinical calcified atherosclerosis: (1) The occlusion site occurs gradually. (2) Calcium deposits are mediated by cells and they progress over time. (3) Acute and chronic inflammation at occlusion sites. (4) Recanalization (new vessel formation) at occlusion sites. These facts indicate that our model bears great similarities to clinical CTO disease. The strategy we apply here is to implant tissue-engineering scaffolds into rabbit femoral arteries and induce the cells on scaffolds to deposit calcium themselves.

In this chapter, we first describe a detailed protocol of scaffold fabrication, growth factor coating on scaffolds, and the initiation of cellular calcification. We then provide easy-to-follow steps to implant cellular constructs into animal arteries using interventional techniques. Finally, we describe the methods to detect calcium in CTOs and the staining approaches to identify other pathological characteristics at the occlusion sites. Additionally, we provide notes to highlight the critical steps in order to successfully carry out this protocol. An animal CTO model generated by the above techniques will provide a useful platform to develop new devices and test novel drugs for treatment of the most severe case of atherosclerotic calcification.

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Author information

Authors and Affiliations

  1. Janey and Dolph Briscoe Division of Cardiology, Department of Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

    Beili Zhu

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  1. Beili Zhu
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Correspondence to Beili Zhu .

Editor information

Editors and Affiliations

  1. Transfusion Services, Monmouth Medical Center, Long Branch, New Jersey, USA

    Arpad Szallasi

  2. Department of Physiology, University of Debrecen Medical and Health Science Center, Debrecen, Hungary

    Tamás Bíró

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Zhu, B. (2012). Atherosclerosis Models with Cell-Mediated Calcification. In: Szallasi, A., Bíró, T. (eds) TRP Channels in Drug Discovery. Methods in Pharmacology and Toxicology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-095-3_4

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  • DOI: https://doi.org/10.1007/978-1-62703-095-3_4

  • Published:

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-094-6

  • Online ISBN: 978-1-62703-095-3

  • eBook Packages: Springer Protocols

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