A dietary approach to increase in-stent stenosis and face validity of a rat model for arterial angioplasty and stenting

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OBJECTIVE: To expedite the investigation of new devices for inhibiting restenosis, we aimed to develop a modified model of arterial angioplasty and stenting in rats that showed greater face validity than the traditional rat model. METHODS: Carotid arteries from Sprague-Dawley rats fed a normal or an atherogenic diet containing a low dose of cholate underwent balloon pre-dilation followed by placement of a bare metal stent. Vessel patency was followed for 28d using ultrasound. Stented vessels were then harvested and were subjected to histologic analysis. Plasma lipid profiles and biomarkers of endothelial dysfunction, inflammation and thrombosis were assessed. RESULTS: There was significant interaction between stenting injury and the atherogenic diet, leading to higher levels of markers for inflammation, platelet activation, and endothelial dysfunction, as well as neointimal hyperplasia, compared with stented rats on normal chow. There was a significant correlation between plasma IL-6 and TXB(2) in stented rats, a relationship which may have contributed to exaggerated vessel remodeling with increased platelet sensitivity. Compared to normal chow, the atherogenic diet also increased fibrin and proteoglycan deposition near stent struts. CONCLUSIONS: Arterial stenting, in combination with the atherogenic diet, led to exacerbated endothelial dysfunction, inflammation, platelet activation, and vascular remodeling compared with stented rats on normal chow. By reproducing key features of clinical restenosis that are lacking in other rat models, this modified rat model may serve as a valuable screening tool to rapidly evaluate new coatings and devices before moving candidates into expensive, more time-consuming rabbit or porcine models.

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