Author(s): Ohnaka M, Marui A, Yamahara K, Minakata K, Yamazaki K,
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Abstract OBJECTIVE: Because microRNA-145 (miR-145) is a specific mediator in the regulation of the proliferation and differentiation of smooth muscle cells, we investigated the effect of miR-145 on the intimal hyperplasia in the rabbit model of vein graft disease using electroporation-mediated gene transfer. METHODS: The right jugular vein of male Japanese white rabbits was harvested and transduced with miR-145-encoding plasmids using an electroporator and then interposed in the carotid artery. At 2 or 4 weeks postoperatively, the venous graft was explanted, and the intimal thickness and intima/media area ratio were evaluated. Furthermore, 3 days after implantation, the myocardin and serum response factors were measured using real-time polymerase chain reaction. At 2 weeks after implantation, immunohistochemical investigations using mature smooth muscle markers, myosin heavy chain smooth muscle-1 and -2, and proliferation marker Ki-67 were performed. RESULTS: MiR-145 transduction significantly reduced the neointimal thickness at both 2 and 4 weeks (2 weeks, 52.1 ± 15.7 vs 113.2 ± 26.9 μm, P < .05, n = 6; 4 weeks, 42.4 ± 4.8 vs 136.5 ± 38.3 μm, P < .05, n = 8), and it also significantly reduced the intima/media area ratio at 4 weeks (0.22 ± 0.04 vs 1.13 ± 0.23, P < .01, n = 8). Additionally, it upregulated the mRNA expression level of myocardin compared with that in the grafts that did not receive gene transfer. Smooth muscle-2 and Ki-67 expression revealed that miR-145 transduced grafts contained more smooth muscle-2-positive mature smooth muscle cells and fewer Ki-67-positive proliferating cells. CONCLUSIONS: Nonviral transduction of miR-145 into the bypass graft could be a novel option for preventing intimal hyperplasia in vein graft disease. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.
This article was published in J Thorac Cardiovasc Surg
and referenced in Journal of Nanomedicine & Nanotechnology