title: Ultrasound-microbubble-mediated intercellular adhesion molecule-1 small interfering ribonucleic acid transfection attenuates neointimal formation after arterial injury in mice.
abstract: OBJECTIVE
  The purpose of this study was to investigate the efficiency of small interfering ribonucleic acid (siRNA) in murine arteries. We transfected it using a nonviral ultrasound-microbubble-mediated in vivo gene delivery system.
  
  
  BACKGROUND
  siRNA is an effective methodology to suppress gene function. The siRNA can be synthesized easily; however, a major obstacle in the use of siRNA as therapeutics is the difficulty involved in effective in vivo delivery.
  
  
  METHODS
  To investigate the efficiency of nonviral ultrasound-microbubble-mediated in vivo siRNA delivery, we used a fluorescein-labeled siRNA, green fluorescent protein (GFP) siRNA, and intercellular adhesion molecule (ICAM)-1 siRNA in murine arteries. Murine femoral arteries were injured using flexible wires to establish arterial injury.
  
  
  RESULTS
  The fluorescein-labeled siRNA and GFP siRNA showed that this nonviral approach could deliver siRNA into target arteries effectively without any tissue damage and systemic adverse effects. ICAM-1 siRNA transfection into murine injured arteries significantly suppressed the development of neointimal formation in comparison to those in the control group. Immunohistochemistry revealed that accumulation of T cells and adhesion molecule positive cells was observed in nontreated injured arteries, whereas siRNA suppressed accumulation.
  
  
  CONCLUSIONS
  The nonviral ultrasound-microbubble delivery of siRNA ensures effective transfection into target arteries. ICAM-1 siRNA has the potential to suppress arterial neointimal formation. Transfection of siRNA can be beneficial for the clinical treatment of cardiovascular and other inflammatory diseases.
authors.affiliation: Department of Advanced Clinical Science and Therapeutics, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, 113-8655 Japan. junichisuzuki-circ@umin.ac.jp
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Suzuki
authors.forename: Masahito
authors.initials: M
authors.lastname: Ogawa
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Takayama
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Taniyama
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Morishita
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Hirata
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Isobe
mesh_terms: D000818:Animals; D001158:Arteries / Q000166:cytology* / Q000000981:diagnostic imaging / Q000293:injuries; D004195:Disease Models, Animal; D015316:Genetic Therapy / Q000379:methods; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D045423:Microbubbles; D018919:Neovascularization, Physiologic / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection / Q000379:methods*; D017539:Tunica Intima / Q000166:cytology / Q000293:injuries; D014463:Ultrasonography
chemical_list: D034741:RNA, Small Interfering; D018799:Intercellular Adhesion Molecule-1