Cardiovascular Research (2010) 85, 38–44 doi:10.1093/cvr/cvp262 A novel mouse model of in situ stenting Janet Chamberlain1*, Mark David C. Crossman1, Julian Wheatcroft1, Nadine Arnold1, Henry Lupton2, Gunn1†, and Sheila Francis1† 1Department of Cardiovascular Science, School of Medicine and Biomedical Sciences, Floor L, Medical School, Beech Hill Road, Shefﬁeld S10 2RX, UK; and 2Brivant Medical Engineering, Galway, Ireland Received 30 January 2009; revised 3 July 2009; accepted 21 July 2009; online publish-ahead-of-print 25 July 2009 Time for primary review: 14 days Aims Animal models of stenting are mostly limited to larger animals or involve substantial abdominal surgery in rodents. We aimed to develop a simple, direct model of murine stenting. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Methods We designed a miniature, self-expanding, nitinol wire coil stent that was pre-loaded into a metal stent sheath. This and results was advanced into the abdominal aorta of the mouse, via femoral access, and the stent deployed. In-stent restenosis was investigated at 1, 3, 7, and 28 days post-stenting. The model was validated by investigation of neointima formation in mice deﬁcient in signalling via the interleukin-1 receptor (IL-1R1), compared with other injury models. Ninety-two per cent of mice undergoing the procedure were successfully stented. All stented vessels were patent. Inﬂammatory cells were seen in the adventitia and around the stent strut up to 3 days post-stenting. At 3 days, an early neointima was present, building to a mature neointima at 28 days. In mice lacking IL-1R1, the neointima was 64% smaller than that in wild-type controls at the 28-day timepoint, in agreement with other models. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conclusion This is the ﬁrst description of a successful model of murine in situ stenting, using a stent speciﬁcally tailored for use in small thin-walled arteries. The procedure can be undertaken by a single operator without the need for an advanced level of microsurgical skill and is reliable and reproducible. The utility of this model is demonstrated by a reduction in in-stent restenosis in IL-1R1-deﬁcient mice. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Keywords Mouse stent model 1. Introduction In vivo models of stenting have been limited to large and medium- sized animals, such as pigs and rabbits, with the porcine model of stenting accepted as the ‘gold standard’ pre-clinical model.1,2 A limitation of the latter is that ‘normal’ pigs do not suffer from ather- osclerosis, even when fed a high-fat diet. In comparison, mice are amenable to genetic manipulation, and ApoE-deﬁcient and LDL receptor-deﬁcient mice are susceptible to atherosclerosis.3,4 In addition, the wide availability of mouse-speciﬁc reagents easily facilitates basic science research. Until very recently, however, mice have not been amenable to stent studies due to size constraints. An arterial stent graft model in the mouse has been described,5 although this is limited by the advanced level of micro- surgical skill required. In addition, this model is not directly com- parable with the routine stent insertion methods used in the clinic. Thus, we aimed to develop a simple, direct model of murine stenting deploying stents in situ. We designed a miniature self-expanding coil stent for use in the mouse abdominal aorta and evaluated the vascular response to injury. Interleukin-1 (IL-1) is an apical mediator in signalling cascades and has previously been shown to be important in response to vas- cular injury in mice6 and pigs.7 In the latter study, an inhibitor of IL-1 administered using osmotic pumps reduced in-stent restenosis * Corresponding author. Tel: þ44 114 2713696, Fax: þ44 114 2268898, Email: j.chamberlain@shefﬁeld.ac.uk † These two individuals are joint senior authors. Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org. The online version of this article has been published under an open access model. 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