Abstract 5894: Arterial Stent Deployment Results in a Time Dependent Increase in Neointima Formation and Delayed Endothelial Cell Repopulation Compared With Balloon Angioplasty
Percutaneous coronary intervention with stenting is the most common means of revascularization in patients with CAD. However, increasing attention has focused on the importance of endothelial cell regeneration after stenting, with important implications for late stent thrombosis and in-stent restenosis. We developed a novel mouse model to evaluate endothelial cell repopulation after stenting. Thoracic aortic segments following either balloon angioplasty alone (BA) or stenting (0.63×2.5mm, 5 cell stainless steel murine stent) from donor ApoE−/− or TIE2-LacZApoE−/− mice were interposition-grafted into the carotid artery of isogenic male recipients using the cuff technique. Mice received oral aspirin (10mg/kg/day) for 5 days prior to surgery and throughout the post-operatively period. Deployment of the stent (1.25mm diameter balloon inflated to 8 atm for 30 sec) resulted in a significant increase in aortic diameter from 0.66±0.03mm to 1.05±0.04 mm, P<0.05. Stented arteries developed a significant time dependent increase in neointima area from post-operative Day 0 to 28 (neointima area 0.07±0.03, 0.25±0.03 and 0.39±0.07 mm2 at Day 7, 14 and 28 respectively, P<0.05). No time dependent difference in media area was observed (P>0.05). Endothelial cell repopulation was assessed en face in stented arteries using TIE2-LacZApoE−/−with endothelial-specific LacZ expression, and confirmed in resin embedded histologic sections. Stent deployment resulted in extensive endothelial cell loss. Partial endothelial cell repopulation (30% of total luminal area) was observed 28 days after stent deployment and increased to 55% repopulation 56 days post-operatively, n=3, compared with a control non-injured aorta. In contrast, endothelial repopulation in vessels that underwent BA alone was increased compared with stented arteries (62 and 76% repopulation at 28 and 56 days post-operatively, respectively). In conclusion, arterial stent deployment results in a time dependent increase in neointima formation and delayed endothelial cell re-population compared with BA. Endothelial cell tracking in genetic mouse models will provide new approaches to test the effects of stenting on endothelial repopulation and the relationship with neointima formation.