Monocyte adhesion to balloon-injured arteries: The influence of endothelial cell seeding

Objective: Deendothelialization of injuries of the artery disrupts normal v ascular homeostasis, affecting both the structural integrity of the blood v essel wall, as well as the interaction of the arterial surface with blood c omponents such as platelets, leukocytes, and circulating proteins. Leukocyt e and, in particular, monocyte recruitment to damaged vessels has been impl icated in the pathogenesis of intimal hyperplasia. We hypothesize that reen dothelialization is an important modulator of monocyte adhesion to healing arterial surfaces. Methods New Zealand white rabbits (n = 20) were subjected to bilateral ilio femoral artery balloon injury. Cultured, autologous venous endothelial cell s (ECs) were immediately seeded onto one vessel, whereas the contralateral artery received medium alone, to accelerate endothelial relining. Vessels w ere harvested (5-9 days after injury for analysis of permeability (Evans Bl ue dye exclusion), endothelial coverage (anti-CD31 immunohistochemistry), m onocyte adhesion (ex vivo binding of (Na2CrO4)-Na-51-labeled monocytic THP- 1 cells), and monocyte recruitment (RAM-11 immunohistochemistry). Results: Improved EC coverage was evidenced by positive staining for CD31 i n the seeded vessels. Vessel wall permeability was markedly reduced in EC-s eeded arteries (29% +/- 10% vs 99% +/- 0% surface Evans blue staining, P < .005), consistent with restoration of a functional endothelial barrier. EC seeding significantly reduced ex vivo THP-1 binding to vessels explanted at a mean of 8 days after injury (45,170 +/- 8939 w 85,994 +/- 16,500 cells/c m(2), P < .05). However, RAM-11 staining revealed no significant difference in overall macrophage accumulation between seeded and control vessels 1 we ek after injury (111 +/- 22 vs 95 +/- 14 cells/section, P =.36). Conclusions: Immediate seeding of a balloon-injured rabbit artery with cult ured ECs results in accelerated restoration of the endothelial lining. At 1 week, barrier function is improved, and the seeded vessel surface is less adhesive to activated monocytes ex vivo, as compared with injured controls. Nonetheless, EC-seeded and nonseeded arteries demonstrate similar total ma crophage accumulation over 1 week. These data suggest that after mechanical arterial injury, endothelial coverage may be one important variable influe ncing leukocyte adhesion.