Abstract
Despite the number of animal models of atherosclerosis, a major limitation in research on mechanisms of plaque rupture is the lack of appropriate atherosclerotic mouse models where lesions develop and progress to a vulnerable and thus rupture-prone phenotype that is typically observed in humans. Most animal models of atherosclerosis typically represent a few but not the full combination of the characteristics seen in human unstable/ruptured plaques. Such characteristics most importantly include a thin and ruptured fibrous cap, plaque inflammation, neovascularization within the plaque (vasa vasorum), plaque hemorrhage, and intravascular (often occlusive) thrombus formation. Ideally, an animal model of plaque instability/rupture would respond to current pharmacological interventions known to reduce the risk of plaque rupture, such as statins. Here we describe a mouse model of plaque instability/rupture that is based on the surgical introduction of a tandem stenosis in the carotid artery. This model results in the formation of unstable atherosclerotic plaques that reflect human plaque pathology. It will allow to further understanding of plaque instability/rupture, to identify the participating factors such as specific proteins, genes and microRNAs, and to develop imaging methods towards the detection of vulnerable, rupture-prone atherosclerotic plaques.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Cheng C, Tempel D, van Haperen R et al (2006) Atherosclerotic lesion size and vulnerability are determined by patterns of fluid shear stress. Circulation 113(23):2744–2753
Slager CJ, Wentzel JJ, Gijsen FJ et al (2005) The role of shear stress in the generation of rupture-prone vulnerable plaques. Nat Clin Pract Cardiovasc Med 2(8):401–407
Cheruvu PK, Finn AV, Gardner C et al (2007) Frequency and distribution of thin-cap fibroatheroma and ruptured plaques in human coronary arteries: a pathologic study. J Am Coll Cardiol 50(10):940–949, doi:S0735-1097(07)01931-6 [pii]10.1016/j.jacc.2007.04.086
Chen YC, Bui AV, Diesch J et al (2013) A novel mouse model of atherosclerotic plaque instability for drug testing and mechanistic/therapeutic discoveries using gene and microRNA Expression Profiling. Circ Res 113(3):252–265. doi:10.1161/CIRCRESAHA.113.301562
Jain MK, Ridker PM (2005) Anti-inflammatory effects of statins: clinical evidence and basic mechanisms. Nat Rev Drug Discov 4(12):977–987, doi:nrd1901 [pii] 10.1038/nrd1901
Finn AV, Nakano M, Narula J et al (2010) Concept of vulnerable/unstable plaque. Arterioscler Thromb Vasc Biol 30(7):1282–1292, doi:30/7/1282 [pii] 10.1161/ATVBAHA.108.179739
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2015 Springer Science+Business Media New York
About this protocol
Cite this protocol
Chen, Y.C., Rivera, J., Peter, K. (2015). Tandem Stenosis to Induce Atherosclerotic Plaque Instability in the Mouse. In: Andrés, V., Dorado, B. (eds) Methods in Mouse Atherosclerosis. Methods in Molecular Biology, vol 1339. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2929-0_23
Download citation
DOI: https://doi.org/10.1007/978-1-4939-2929-0_23
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-2928-3
Online ISBN: 978-1-4939-2929-0
eBook Packages: Springer Protocols