ENDOTHELIAL-CELL SEEDING FAILS TO ATTENUATE INTIMAL THICKENING IN BALLOON-INJURED RABBIT ARTERIES

Background: Restenosis of arteries or bypass grafts after vascular rec onstruction is a common clinical entity that significantly limits long -term patency. This process, termed intimal hyperplasia (IH), is chara cterized by smooth muscle cell proliferation in the intima and subsequ ent accumulation of intercellular matrix. This study was designed to t est the hypothesis that endothelial cell (EC) seeding of acutely injur ed arteries accelerates reendothelialization of the flow surface and l imits the development of IH. Methods: ECs were harvested from jugular veins of New Zealand white rabbits (n = 13) and were amplified in tiss ue culture. Each animal subsequently underwent bilateral balloon cathe ter injury of the iliofemoral arteries; one side was immediately seede d with cultured autologous ECs at supraconfluent density, whereas the contralateral vessel served as a nonseeded control. Animals were kille d 33 +/- 5 days after balloon injury. Intimal thickening was quantitat ed on histologic sections of vessels (three sections per vessel, total of 60 sections) and percent endothelialization was assessed by SEM; m easurements were obtained by use of computer-aided morphometry perform ed by a blinded observer. Data were analyzed by use of a paired t test for comparison between seeded and control vessels. Results: Seeded ve ssels exhibited a greater degree of reendothelialization (93.9% +/- 7. 6% of the surface) than their unseeded counterparts (65.1% +/- 22.5%, p < 0.01). Intimal cross-sectional area and the ratio of intimal area to medial area were not significantly different between seeded and con trol vessels (intima: 0.32 +/- 0.19 vs 0.37 +/- 0.11 mm(2), p = 0.28; intimal area to medial area ratio: 0.84 +/- 0.35 vs 1.02 +/- 0.2, p = 0.24). Conclusions: We conclude that seeding with autologous venous EC s accelerated restoration of the endothelial monolayer but failed to a ttenuate IK in balloon-injured rabbit arteries. Further studies are ne cessary to determine the functional properties of seeded endothelium a nd to examine the effect of EC seeding on intimal thickening in other clinically relevant models.