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J Thorac Cardiovasc Surg. 2014 Aug;148(2):676-82.e2. doi: 10.1016/j.jtcvs.2013.11.054. Epub 2013 Dec 31.

Effect of microRNA-145 to prevent vein graft disease in rabbits by regulation of smooth muscle cell phenotype.

Author information

1
Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
2
Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan. Electronic address: marui@kuhp.kyoto-u.ac.jp.
3
Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center, Osaka, Japan.
4
Department of Pharmacoepidemiology, Kyoto University Graduate School of Medicine and Public Health, Kyoto, Japan.

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.

PMID:
24507892
DOI:
10.1016/j.jtcvs.2013.11.054
[Indexed for MEDLINE]
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