878. Overexpression of Fibromodulin Inhibits Neointima Formation in Cultured Human Saphenous Veins

Introduction: The success of coronary artery bypass grafting (CABG) is limited by poor long-term graft patency. Saphenous vein (SV) is the most commonly used conduit for CABG with a high failure rate due to intimal thickening and superimposed atherosclerosis. In the absence of any effective pharmacological therapies, late vein graft failure has been identified as a putative target for gene therapy. Two small leucine-rich proteoglycans, decorin and fibromodulin, possess TGF-β 1 -antagonist activity in vitro and in vivo. Local overexpression of decorin reduces neointima formation in response to arterial injury in animal models. However fibromodulin is a more effective competitor for TGF-β binding than decorin. The purpose of this study was to evaluate the ability of adenoviral-mediated gene transfer of bovine fibromodulin to inhibit neointima formation in an ex vivo model of vascular injury.Methods: Excess surgically prepared SV segments from patients undergoing CABG were cannulated and the luminal surface was exposed to PBS or 10 8 iu of 1 of 2 adenoviruses for 1 hour: Ad5-lacZ (expressing β-galactosidase) or Ad5-FMOD (expressing bovine fibromodulin). The vein segments were incised longitudinally and cultured luminal surface uppermost. Segments cultured for 14 days were fixed and paraffin-embedded. Sections stained for elastic tissues underwent morphometric assessment and the area of neointima and maximum neointimal thickness and I/M ratio were measured in each segment.Results: (See table 1) Mean neointimal area (mm 2 ) in vein segments exposed to Ad5-FMOD was significantly less than in PBS or lacZ groups (P=0.0003 by ANOVA). I/M ratio and maximum neointimal thickness (μm) were also significantly reduced in veins exposed to Ad5-FMOD compared to controls (P=0.008 & 0.018 respectively). Post-hoc analysis revealed that maximum neointimal thickness and I/M ratio did not differ significantly between PBS and lacZ groups, although neointimal area in lacZ vessels was significantly smaller than that in the PBS group (P