title: Effect of microRNA-145 to prevent vein graft disease in rabbits by regulation of smooth muscle cell phenotype.
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.
authors: Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Motoaki
authors: M
authors: Ohnaka
authors: Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan. Electronic address: marui@kuhp.kyoto-u.ac.jp.
authors: Akira
authors: A
authors: Marui
authors: Department of Regenerative Medicine and Tissue Engineering, National Cerebral and Cardiovascular Center, Osaka, Japan.
authors: Kenichi
authors: K
authors: Yamahara
authors: Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Kenji
authors: K
authors: Minakata
authors: Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Kazuhiro
authors: K
authors: Yamazaki
authors: Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Motoyuki
authors: M
authors: Kumagai
authors: Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Hidetoshi
authors: H
authors: Masumoto
authors: Department of Pharmacoepidemiology, Kyoto University Graduate School of Medicine and Public Health, Kyoto, Japan.
authors: Shiro
authors: S
authors: Tanaka
authors: Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Tadashi
authors: T
authors: Ikeda
authors: Department of Cardiovascular Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors: Ryuzo
authors: R
authors: Sakata
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D017536:Carotid Artery, Common / Q000601:surgery; D002454:Cell Differentiation; D049109:Cell Proliferation; D004195:Disease Models, Animal; D018274:Electroporation; D005786:Gene Expression Regulation; D015316:Genetic Therapy; D006083:Graft Occlusion, Vascular / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D006965:Hyperplasia; D007150:Immunohistochemistry; D007601:Jugular Veins / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D058426:Neointima; D010641:Phenotype; D011817:Rabbits; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014161:Transduction, Genetic / Q000379:methods
chemical_list: D015415:Biomarkers