Vascular endothelial growth factor and heparin in a biologic glue promotes human aortic endothelial cell proliferation with aortic smooth muscle cell inhibition

Abstract

Incomplete luminal endothelialization may contribute to small diameter vascular graft failure. Vascular endothelial growth factor (VEGF) can be used to stimulate endothelialization without provoking smooth muscle cell (SMC) proliferation. Heparin and VEGF in a fibrin glue (FG) were investigated for their ability to promote selective human aortic endothelial cell (HAEC) proliferation and human aortic smooth muscle cell (HASMC) inhibition. HAECs and HASMCs were seeded on FG containing VEGF (2.5, 10, 30, 100 ng/ml) or VEGF and heparin (5, 50, 500 units/ml). Proliferation assays were performed with tritiated thymidine on days 1 and 3. Results were analyzed by ANOVA, with p < or = 0.05 significant. HAEC proliferation on FG with 10, 30, and 100 ng/ml VEGF was significantly greater than FG alone at days 1 and 3. The addition of 50 units/ml heparin to VEGF significantly increased HAEC proliferation to greater than FG with VEGF alone at day 1. Human aortic SMC proliferation was not stimulated by the addition of VEGF. The addition of 5, 50, and 500 units/ml heparin significantly inhibited HASMC proliferation regardless of VEGF concentration. VEGF at 10 ng/ml combined with heparin at 50 units/ml exhibited maximal stimulation of HAECs with inhibition of HASMCs. VEGF and heparin in a biologic glue may improve patency by selectively promoting HAEC proliferation without HASMC growth on synthetic vascular bypass grafts.