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) following post-thrombotic iliac vein stent placement and characterize histopathological changes of tissue within the stented vein.

MATERIALS AND METHODS: Iliac vein thrombosis was induced via balloon occlusion and thrombin injection in eight male Boer goats. Mechanical thrombectomy and iliac vein stent placement were performed 3 days after thrombosis induction. Restenosis was evaluated via 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 eight 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 were 15%-33%. At 8 weeks, the degree of ISR were 21%-32% in three goats, and stent occlusion was observed in one goat. At 1 week, the neointima was dominated by 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.

CONCLUSION: In the goat model, post-thrombotic neointimal hyperplasia in the venous stent may result from time-dependent 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.