Endothelial cell seeding influences lesion development following arterial injury in the cholesterol-fed rabbit

Objective: A functionally intact endothelial monolayer is thought to be critical for the adaptive process of vascular remodeling. This study was undertaken to examine the hypothesis that endothelial restoration is a critical determinant of remodeling after balloon angioplasty. Methods: Rabbits (N=12) were fed a cholesterol-supplemented diet (0.5%) and were subjected to bilateral balloon catheter injury of the iliofemoral arteries. At the time of injury, autologous venous endothelial cells (ECs) were implanted on one artery; the contralateral vessel served as control. A mean of 42 days after injury, arteriography was performed, followed by vessel harvest and histologic analysis. Results: High grade (≥70%) stenoses or occlusion were present in 55% of control and none of the EC-seeded arteries. EC-seeding was associated with improved mean (1.0±0 vs. 0.7±0.1, P<0.001) and minimal (0.7±0.1 vs. 0.4±0.1, P<0.001) luminal diameters by angiography. Seeded arteries demonstrated decreased medial area (0.69±0.04 vs. 1.04±0.09 mm², P<0.001), a more uniform range of final lumen area (P<0.0001), and a positive remodeling index. Neointimal area was not significantly different. Stenoses were characterized primarily by larger neointimal area (2.02±0.18 vs. 1.38±0.09 mm², stenotic vs. non-stenotic, P<0.005). Final lumen area was strongly influenced by both neointimal growth and vessel remodeling. Conclusions: These data support the concept that endothelial restoration is a critical determinant of the outcome of vessel wall repair, particularly in the context of hypercholesterolemia.