Abstract 306: Transfected Early Growth Response Gene-1 DNA Enzyme Attenuates Autogenous Vein Graft Intimal Hyperplasia in vivo

Abstract

Introduction Early growth response gene-1 (Erg-1) functions centrally in cell proliferation. We hypothesized that introduction of a novel Egr-1 DNA enzyme (EDRz) via liposomes into the vein graft would attenuate occlusive SMC proliferation and intimal hyperplasia. Methods Rat jugular vein was anastomosed to the infrarenal abdominal aorta end-to-end. EDRz (n=90) was applied to the graft vein adventitia (no therapy control; n=90). Animals were harvested at 1, 2, and 6hr, and 1, 3, 7, 14, 28, and 42d (10 EDRz/10 control per time point). Analyses included light microscopy (morphology), fluorescence (EDRz transfection), RT-PCR and in situ hybridization (Egr-1 mRNA), and Western blot and immunohistochemistry (Egr-1 protein). Results EDRz localized to the vein graft media early; Egr-1 protein was in medial SMCs, monocytes, and ECs; treated grafts had no detectable Egr-1 RNA or protein by 7d. VSMC proliferation (p<0.01 from 3-42d) and intimal thickness were attenuated by EDRz (p<0.01 from 7-42d; Fig ). Conclusions EDRz reduces Egr-1 expression, SMC proliferation, and intimal hyperplasia in autogenous vein grafts. EDRz offers a novel approach to enhance vein graft durability. Figure. The result of thickness of intimal hyperplasia in vein graft and EDRz transfection after 1