Abstract 18531: Impact of MicroRNA-145 to Prevent Vein Graft Disease in Rabbit by Regulation of Smooth Muscle Cell Phenotype

Abstract

Backgrounds Intimal hyperplasia is the major cause of vein graft disease. Smooth muscle cell (SMCs) proliferation and migration into the intima are key mechanism in this process. Recent studies have reported that microRNA-145(miR-145) is a specific mediator in the regulation of proliferation, differentiation, and phenotype of SMCs. In this study, we sought to investigate the impact of miR-145 to intimal hyperplasia in rabbit model of vein graft disease using electropolation mediated gene transfer. Methods and Results Right jugular vein of male Japanese white rabbit was harvested (15mm) and endothelial cells of the graft were injured by balloon catheter. The graft was interposed in ipsilateral jugular artery in reversed fashion (Control group). Alternatively, harvested jugular vein was transduced with miR-145 encoding plasmids by electroporator after balloon injury, and then interposed in ipsilateral jugular artery in the same fashion (miR-145 group). Two weeks after surgery, venous graft was explanted. Four sections were obtained and each section was stained with both hematoxylin and eosin, and the elastica van Gieson method for elastic fiber staining. Neointima formation was quantified on cross sections of vein graft and reendothelialization and intima/media area ratio were evaluated. Optimal condition of the electroporator (Figure 1a) was confirmed by DsRed immunostaining (Figure 1b: positive red fluorescence on inner surface of the graft 1c: DsRed monoclonal antibody staining). Reendothelialization was significantly reduced in miR-145 transduced grafts at 2 weeks (Figure 1d, 1e). Arrowheads indicate the internal lamina. Intima/media area ratio was significantly lower in the miR-145 group compared to the control group (0.062±0.011 vs. 0.365±0.281, p=0.03) . Conclusion Transduction of miR-145, which specifically regulates smooth muscle cell phenotype, into the bypass graft may be a novel option to prevent intimal hyperplasia in vein graft disease.