Abstract 15693: A Novel Rabbit Model of Plaque Erosion With Spontaneous Atherothrombotic Occlusion
Background: Plaque erosion is known to be a major cause of coronary atherothrombosis that leads to acute coronary syndrome. However, the mechanism of atherothrombosis on plaque erosion remains poorly understood, because of the lack of appropriate animal models. Here we report a first animal model of plaque erosion with spontaneous atherothrombotic occlusion.
Methods and Results: The occurrence of atherothrombosis was examined in femoral arteries of Japanese white rabbits fed a high cholesterol diet by high-resolution ultrasonography (Fig. A). Balloon injury of femoral arteries caused neointima formation, but did not result in atherothrombosis. Importantly, the addition of angiotensin II infusion caused spontaneous atherothrombotic occlusion of the injured arteries at median 5.5 weeks (6/6 animals, Fig. B). After the occurrence of acute thrombotic occlusion, the presence of thrombosis was confirmed by angiographic and histopathologic examination. Histochemical analysis in the atherothrombotic sites revealed; 1) no severe stenosis (% stenosis: 49±7), 2) no plaque rupture or lipid core, and, 3) no PECAM1-positive endothelial layer. Interestingly, there were smooth muscle-like cells (αSMA+/SM1, SM2, SMemb and calponin-) with tissue factor expression at the neointima-thrombus interface (NTI) (Fig. C), and some of these cells were positive for RAM-11. Oral treatment with dabigatran (10 mg/kg/day) or rivaroxaban (3 mg/kg/day) combined with aspirin (20 mg/kg/day) prevented atherothrombotic occlusion in this model. (Fig. B)
Conclusion: We established for the first time an appropriate and valid animal model of spontaneous atherothromobotic occlusion due to plaque erosion in rabbits, which mimicked the pathological features of plaque erosion seen in human coronary arteries. This model may provide a clue to a mechanistic understanding of plaque erosion and to the development of drugs that prevent or delay plaque erosion and subsequent atherothrombosis.
- © 2013 by American Heart Association, Inc.