EFFECT OF RETROVIRAL TRANSDUCTION ON HUMAN ENDOTHELIAL-CELL PHENOTYPEAND ADHESION TO DACRON VASCULAR GRAFTS

Purpose: Retroviral transduction for genetic enhancement of endothelia l cell (EC) antithrombotic phenotype offers potential for improving th e clinical success of vascular graft seeding; however, application of this technique may bring concomitant alteration in cell functionality. Methods: Human microvascular ECs were transduced with a retroviral ve ctor encoding for the marker gene beta-galactosidase. Transduced endot helial cells (rtECs) and nontransduced endothelial cells (ntECs) were evaluated by flow cytometry for expression of intercellular adhesion m olecule (ICAM)-1 and tissue factor (TF) on both smooth (coverslips) an d graft (Dacron, 6 mm inside diameter) surfaces under static and shear exposed conditions. Graft EC retention was measured after 6-hour puls atile perfusions. Platelet and neutrophil adherence was measured on pe rfused coverslips. Results: Lower levels of ICAM-1 were expressed by r tECs on coverslips under both static (p < 0.01 vs static ntECs) and sh ear exposed conditions (p < 0.01 vs static and shear ntECs). According ly, fewer polymorphonuclear leukocytes adhered to rtEC monolayers (p < 0.01 vs ntECs). No difference in ICAM-1 and TF expression by static g raft seeded rtECs and ntECs was observed. However, graft-seeded rtECs that were exposed to wall shear stress displayed less TF than sheared ntECs (p < 0.05). Transduction did not affect EC retention to the shea red graft surface. Conclusions: These data suggest that retroviral tra nsduction does not elicit a prothrombotic/proinflammatory phenotype, r ather indices of these states appear in some conditions to be reduced. Further, transduction does not adversely affect EC adherence to Dacro n graft surfaces under arterial hemodynamics.