title: Small interfering RNA targeting nuclear factor kappa B to prevent vein graft stenosis in rat models.
abstract: BACKGROUND
  Intimal hyperplasia plays an important role in vein graft stenosis. Inflammatory injury, especially nuclear factor kappaB (NF-κB) gene activation, is highly involved in stenosis progression. We examined whether neointimal hyperplasia and vein graft stenosis could be inhibited by silencing the NF-κB gene with small interference RNA (siRNA).
  
  
  METHODS
  Sixty adult male Sprague-Dawley rats were randomly divided into a normal vein group, a vein graft group, a scrambled siRNA group, and an NF-κB siRNA group. We performed reverse interpositional grafting of the autologous external jugular vein to the abdominal aorta. Vein grafts were treated with liposome and gel complexes containing NF-κB siRNA or scrambled siRNA. The levels of monocyte chemoattractant protein -1, tumor necrosis factor-α, and NF-κB p65 in vessel tissues were evaluated after surgery for content of proliferating cell nuclear antigen (PCNA) and vascular wall thickness.
  
  
  RESULTS
  NF-κB siRNA treated vein graft showed less neointimal formation and fewer positive PCNA cells (P < .05). In addition there were lower levels of, NF-κB p65 protein and of inflammatory mediators (P < .05) compared with the vein graft group.
  
  
  CONCLUSIONS
  Our study suggested that siRNA transfection suppressed NF-κB expression, reduced inflammatory factors, lessened neointimal proliferation, and suppressed PCNA.
authors: Department of Cardiovascular Surgery, QiLu Hospital, Shandong University, Jinan, Shandong Province, China.
authors: X B
authors: XB
authors: Meng
authors: X L
authors: XL
authors: Bi
authors: H L
authors: HL
authors: Zhao
authors: J B
authors: JB
authors: Feng
authors: J P
authors: JP
authors: Zhang
authors: G M
authors: GM
authors: Song
authors: W Y
authors: WY
authors: Sun
authors: Y W
authors: YW
authors: Bi
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D003251:Constriction, Pathologic; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D015316:Genetic Therapy / Q000379:methods*; D006083:Graft Occlusion, Vascular / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D006965:Hyperplasia; D007601:Jugular Veins / Q000378:metabolism / Q000473:pathology / Q000637:transplantation*; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D058426:Neointima; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D019394:Ki-67 Antigen; D016328:NF-kappa B; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C498145:Rela protein, rat; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha