Rat Abdominal Aorta Stenting: A New and Reliable Small Animal Model for In-Stent Restenosis

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Abstract
A high throughput animal model may enhance pathophysiological studies to mechanisms of in-stent restenosis (ISR). More and appropriate antibodies and transgenic and knockout strains are available in rats. Consequently, a model for ISR in the rat would be convenient for pathobiological studies. Here we present the full characteristics of a rat ISR model suitable for high throughput stent research.The abdominal aorta of rats was separated from surrounding tissue and a BeStenttrade mark 2 or a Cyphertrade mark sirolimus-eluting stent was locally inserted. After 1, 3, 7, 28 and 56 days, the aortas were harvested, fixed, embedded and cut. Morphometric analysis was performed and inflammation scored.The neointimal area increased to a maximum after 28 days (0.55 +/- 0.08 mm(2)). Subsequently, the neointimal area slightly decreased. The injury score and the neointimal area were linearly correlated (r = 0.85, p < 0.01). Thrombus formation was present after 1 day. Leukocyte adherence was evident after 1 day, maximal after 3 days (93 +/- 21 cells/section) and decreased thereafter. The inflammation score increased after 3 days to a maximum after 7 days (1.37 +/- 0.06) and declined thereafter. After 28 days the Cypher sirolimus-eluting stent decreased the stenosis in comparison to the BeStent 2 (10.2 +/- 0.85 vs. 18.0 +/- 2.0%, respectively, p < 0.01).Stent deployment in the rat abdominal aorta results in thrombus formation, inflammation and neointimal formation. Moreover, there is a linear correlation between the injury score and the neointimal area. These responses resemble ISR events as seen in other animal models. Moreover, a known anti-restenotic stent also reduces neointimal formation in this model. Rat abdominal aorta stenting is a promising animal model for ISR, it is suitable for testing commercially manufactured stents and studying the pathophysiology of ISR.

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