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Cardiovascular Research 2002 53(2):502-511; doi:10.1016/S0008-6363(01)00486-2
© 2002 by European Society of Cardiology
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Copyright © 2001, European Society of Cardiology

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

Michael S Contea,d,*, Guy A VanMetera,d, Lee M Aksta, Tracy Clemonse, Michael Kashgarianc and Jeffrey R Benderb,d

aDepartment of Surgery, Yale University School of Medicine, New Haven, CT, USA
bDepartment of Medicine (Cardiology), Yale University School of Medicine, New Haven, CT, USA
cDepartment of Pathology, Yale University School of Medicine, New Haven, CT, USA
dThe Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT, USA
eHarvard University School of Public Health, Boston, MA, USA

* Corresponding author. Department of Surgery, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115, USA. Tel.: +1-617-732-6816; fax: +1-617-730-2876 mconte{at}partners.org

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.

KEYWORDS Angioplasty; Arteries; Endothelial function; Restenosis; Cholesterol


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