803-3 Influence of Presence or Absence of Medial Necrosis on Endothelial Regeneration and Intimal Hyperplasia in the Rabbit Carotid Artery

Abstract

Interventional injury induced intimal hyperplasia (IH) involves smooth muscle cell proliferation which may be limited by endothelial cell (ECI regeneration. We hypothesized that EC-regeneration (ECR) modulates IH. To create different ECR's we induced EC removal with 100% media necrosis (2F Fogarty balloon, 5 cm) and without media necrosis (prolene loop, 5 cm) in the rabbit carotid artery. After termination at 3, 7, 21 or 42 days, the artery was divided in segments which were alternately processed for paraffin- and frozen sections. ECR was assessed with an antibody to CD31 and expressed as percentage coverage. Proliferating cells were identified with an antibody to the nuclear antigen Ki-67 and scored as percentage positive cells. The crosssectional IH area (IHA, mm 2 ) was measured morphometrically from elastin stained sections. Wall coverage (%) with CD31 positive cells, IHA (mm 2 ) (mean ± sem, * = p < 0.05, † = P < 0.001, Fogarty balloon (BAL) versus loop): n ECR,3d ECR,7d ECR,21d ECR,42d IHA,7d IHA,21d IHA,42d BAL 7 3 ± 2 57 ± 14 61 ± 5 82 ± 11 0.01 ± 0.01 0.20 ± 0.01 * 0.26 ± 0.03 * loop 7 8 ± 4 81 ± 10 93 ± 4 100 ± 0 0.01 ± 0.01 0.09 ± 0.04 0.08 ± 0.02 From 3–42 days, ECR was enhanced in loop versus balloon injured arteries (P < 0.001, ANOVA). At 3 and 7 days, more medial proliferation was found after balloon than after loop injury (3d: 46.2 ± 8.8% versus 0.2 ± 0.1%, 7d: 18.5 ± 6.4% versus 1.0 ± 0.4%; p < 0.01, ANOVA). In the same period, abundant adventitial proliferation was found after balloon injury which was entirely absent after loop injury. Endothelial cell regeneration is slower over a damaged than over a normal media. This retarded endothelial cell regeneration may contribute to enhanced intimal hyperplasia.