VASCULAR ENDOTHELIAL GROWTH-FACTOR AND HEPARIN IN A BIOLOGIC GLUE PROMOTES HUMAN AORTIC ENDOTHELIAL-CELL PROLIFERATION WITH AORTIC SMOOTH-MUSCLE CELL-INHIBITION

Background. Incomplete luminal endothelialization may contribute to sm all diameter vascular graft failure. Vascular endothelial growth facto r (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 hum an aortic endothelial cell (HAEC) proliferation and human aortic smoot h muscle cell (HASMC) inhibition. Methods. HAECs and HASMCs were seede d 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 tritiat ed thymidine on days 1 and 3. Results were analysed by ANOVA, with p l ess than or equal to 0.05 significant. Results. HAEC proliferation on FG with 10, 30, and 100 ng/ml VEGF significantly increased HAEC prolif eration 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 prol iferation regardless of VEGF concentration. Discussion. 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 glu e may improve patency by selectively promoting HAEC proliferation with out HASMC growth on synthetic vascular bypass grafts.