Histological Features of In-Stent Restenosis after Iliac Vein Thrombus Removal and Stent Placement in a Goat Model

Purpose: To establish an animal model for in-stent restenosis (ISR) after postthrombotic iliac vein stent placement and characterize histopathological changes in tissue within the stented vein. Materials and Methods: Iliac vein thrombosis was induced using balloon occlusion and thrombin injection in 8 male Boer goats. Mechanical thrombectomy and iliac vein stent placement were performed 3 days after thrombosis induction. Restenosis was evaluated by venography and optical coherence tomography (OCT) at 1 and 8 weeks after stent placement, and stent specimens were taken for pathological examination after the animals were euthanized. Results: Thrombosis induction was successful in all 8 goats, with >80% iliac vein occlusion. After thrombus removal, OCT revealed considerable venous intimal thickening and a small number of mural thrombi. Neointimal hyperplasia with thrombus formation was observed in all goats 1 week after stent implantation; the degree of ISR was 15%-33%. At 8 weeks, the degree of ISR was 21%-32% in 3 goats, and stent occlusion was observed in 1 goat. At 1 week, the neointima predominantly consisted of fresh thrombi. At 8 weeks, proliferplastic fibrotic tissue and smooth muscle cells (SMCs) were predominant, and the stent surfaces were endothelialized in 2 of 3 goats and partially endothelialized in 1 goat. Conclusions: In the goat model, postthrombotic neointimal hyperplasia in the venous stent may result from timedependent thrombus formation and organization, accompanied by migration and proliferation of SMCs, causing ISR. These results provide a basis to further explore the mechanism of venous ISR and promote the development of venous stents that reduce neointimal hyperplasia.