Ultrasound-microbubble-mediated intercellular adhesion molecule-1 small interfering ribonucleic acid transfection attenuates neointimal formation after arterial injury in mice.
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.
Suzuki
Jun-ichi
J
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
Ogawa
Masahito
M
Takayama
Kiyoshi
K
Taniyama
Yoshiaki
Y
Morishita
Ryuichi
R
Hirata
Yasunobu
Y
Nagai
Ryozo
R
Isobe
Mitsuaki
M
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
D034741:RNA, Small Interfering; D018799:Intercellular Adhesion Molecule-1