title: Bortezomib reduces neointimal hyperplasia in a rat carotid artery injury model.
abstract: OBJECTIVE
  The ubiquitin-proteasome system is the major intracellular protein degradation pathway in the eukaryotic cells. Bortezomib inhibits 26S proteasome-induced I-κBα degradation and suppresses nuclear factor-kappa B (NF-κB) activation. We examined the effect of bortezomib on neointima formation after of a rat carotid artery balloon injury.
  
  
  METHODS
  After carotid artery balloon denudation, bortezomib was immediately administered by tail vein injection (systemic treatment) and by using an F-127 pluronic gel (perivascular treatment). Two weeks after the injury, we compared the degree of neointima formation in the carotid artery and the tissue expression patterns of NF-κB and I-κBα.
  
  
  RESULTS
  The systemic treatment group exhibited a 29% reduction in neointima volume at two weeks after the balloon injury. On the western blot analysis, the bortezomib group exhibited an increased I-κBα expression, which suggested the inhibition of I-κBα degradation. On immunofluorescence analysis, the nuclear import of NF-κB was clearly decreased in the systemic bortezomib group. The perivascular bortezomib treatment group exhibited a significant reduction in the neointimal area (0.21±0.06 mm(2) vs. 0.06±0.01 mm(2), p<0.05), the neointima/media area ratio (1.43±0.72 vs. 0.47±0.16, p<0.05) and the % area stenosis (45.5±0.72% vs. 14.5±0.05%, p<0.05) compared with the control group. In situ vascular smooth muscle cell proliferation at 2 days after the injury was significantly inhibited (24.7±10.9% vs. 10.7±4.7%, p<0.05).
  
  
  CONCLUSIONS
  Bortezomib suppressed NF-κB activation through the inhibition of I-κBα degradation, and significantly reduced neointima formation in a rat carotid artery injury model. These data suggested that bortezomib represented a new potent therapeutic agent for the prevention of restenosis.
authors.affiliation: Department of Medicine, College of Medicine, Jeju National University, Jeju, Korea.
authors.forename: Ki-Seok
authors.initials: KS
authors.lastname: Kim
authors.forename: Song Yi
authors.initials: SY
authors.lastname: Kim
authors.forename: Joon Hyeok
authors.initials: JH
authors.lastname: Choi
authors.forename: Seung Jae
authors.initials: SJ
authors.lastname: Joo
authors.forename: Dong Woon
authors.initials: DW
authors.lastname: Kim
authors.forename: Myeong Chan
authors.initials: MC
authors.lastname: Cho
keywords: Angioplasty; Coronary restenosis; Nuclear factor kappa B; Proteasome