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.
CTSNet classification
23.1
33
33.1
Abbreviations and Acronyms
GFP
green fluorescent protein
miR-145
microRNA-145
SMC
smooth muscle cell
SM-1
smooth muscle-1
SM-2
smooth muscle-2
SRF
serum response factor
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This work was supported by a grant for Scientific Research (B) (grant 22390265) from the Japanese Ministry of Education, Culture, Sports, Science, and Technology.
Disclosures: Authors have nothing to disclose with regard to commercial support.