Abstract 653: Development of Advanced Atherosclerotic Plaque by Injection of Inflammatory Proteins in Mini-pig Model

Abstract

Objective: Appropriate animal models of atherosclerotic plaque are crucial for the investigation of the pathophysiology of atherosclerosis, as well as for the evaluation of the efficacy and safety of vascular devices. Therefore, we aimed to develop a novel animal model that would be suitable for the study of the advanced atherosclerotic lesions in vivo. Methods: Atherosclerotic plaque was induced in 32 sites of 8 mini-pigs by combining a high cholesterol diet, endothelial denudation, and injection into the vessel wall with either saline or inflammatory proteins (high-mobility group protein B1 [HMGB1] and tumor necrosis factor [TNF]-α) using a Cricket™ Micro-infusion catheter. In vivo imaging with optical coherence tomography (OCT) was performed to detect the plaque characteristics at follow-up after 10 weeks. All tissues were harvested for histological evaluation. Results: Intima area/plaque area tended to be higher in the HMGB1, and TNF-α groups compared to the saline injected group (p=0.015). Advanced plaques were more frequently observed in the group injected with inflammatory proteins. High degree inflammation occurred in inflammatory protein injected group compared to saline injected group it immunohistochemistry stain using HMGB1 (p<0.001), RAGE (p=0.003), TNF-α antibody (p<0.001) and CD68 antibody (p=0.005). Quantitative imaging evaluation at minimal lumen diameter and percentage of diameter stenosis were also not significantly different among all group. OCT demonstrated that lipid rich plaques were more frequently detected in the inflammatory protein group (saline group: 2/11 [18%], HMGB1 group: 9/11 [82%] and TNF-α group: 5/10 [50%]). Conclusion: Direct injection of inflammatory proteins into the vessel wall significantly increased inflammation occurrence and induced lipid rich plaques. These data indicate that this mini-pig model of atherosclerotic lesion formation via direct injection of pro-inflammatory proteins into the vessel wall is useful for in vivo studies investigating atherosclerosis. Key words: mini-pig model, atherosclerosis, balloon injury, inflammatory protein