Abstract 13860: An Unique Animal Model of Spontaneous Atherothrombotic Occlusion due to Plaque Erosion at Femoral Arteries of Atherosclerotic Rabbits Infused with Angiotensin II
Background: Plaque erosion is known to be a major cause of coronary atherothrombosis that leads to acute coronary syndrome. However, the mechanism of 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 with high cholesterol diet by high-resolution ultrasonography (Vevo 2100, VISUALSONICS Inc.) (Fig. A). Balloon injury of femoral arteries caused neointima formation that consist from de-differentiated (αSMA+/SM1+/SM2-) smooth muscle cells (SMCs), 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 especially immature SMCs (αSMA+/SM1-/SM2-) with tissue factor expression at the neointima-thrombus interface (NTI) (Fig. C). Oral treatment with aspirin (20 mg/day) and dabigatran (10 mg/kg/day) prevented atherothrombotic occlusion (0/5 animals, P< 0.001).
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.
- © 2012 by American Heart Association, Inc.