The natural history of arterial thrombus healing after superficial plaque erosion in an atherosclerotic rabbit model

Abstract Aim To pathologically elucidate the natural history of thrombus healing after endothelial injury in superficial erosion of atherosclerotic plaque. Methods To induce atherogenesis, 12 white rabbits underwent iliac artery balloon injury and were subsequently fed an atherogenic diet. Four weeks later, to induce endothelial injury, staurosporine (a serine-threonine kinase inhibitor that induces endothelial apoptosis) was locally administered via over-the-wire balloon catheter to the atherosclerotic iliac arteries. Four rabbits were euthanized at 1,2 and 3-week post-procedure, respectively. The iliac arteries were harvested and cut every 3 mm intervals. The ring-shaped sections were pathologically examined by hematoxylin-eosin staining and immunostaining. Results Thrombus formation was observed in 6 of 12 rabbits. Representative pathological images of arterial thrombi at 1,2 and 3 weeks post-endothelial injury are shown in Figure. In the rabbits at 1-week, small thrombi formed and inflammatory cells aggregated. At 2-week, the thrombi expanded, contained fibrin and platelets, and some smooth muscle cells were migrating and proliferating, suggesting that organization had begun. At-3 week, additional platelet- and fibrin-based thrombi had formed on the luminal surface of the healed thrombus, leading to arterial occlusion. Conclusion Plaque erosion can lead to arterial occlusion through repeated healing and recurrence over several weeks.The natural history of arterial thrombus