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 (greater than or equal to70%) 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 mm(2), 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 mm(2), 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. (C) 2002 Elsevier Science B.V. All rights reserved.