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Intramural delivery of bortezomib inhibits restenosis following arterial injury.

BACKGROUND
Several studies have demonstrated that the proteasome inhibitors prevent restenosis following arterial injury. The proteasome inhibitor bortezomib shows anti-inflammatory and antiproliferative effects. Here, we evaluate the efficacy of bortezomib in inhibiting the restenosis following arterial injury and the effect on nuclear factor kappa B (NF-kappaB) and p27.


METHODS
An injured iliac artery rabbit model was established by balloon over-stretching. Rabbits were intramurally infused with bortezomib or normal saline by a transport coronary dilatation catheter in the bortezomib (n = 20) or control (n = 20) groups, respectively, and they were sacrificed on the 7th or 21th day following the arterial injury. Neointimal area was measured by computer analysis of photomicrographs, while expression of NF-kappaB and of p27 on day 7 were evaluated by Western blotting and immunohistochemistry, respectively.


RESULTS
Expression of p27 (56.10 ± 3.03% vs. 10.24 ± 0.60%, p < 0.05) was significantly higher while that of NF-kappaB (0.44 ± 0.02 vs. 0.70 ± 0.03, p < 0.05) was significantly lower in the bortezomib group than in control group on day 7 after arterial injury. Neointimal formation was significantly lower in the bortezomib group on day 21 after arterial injury (0.67 ± 0.03 vs. 1.30 ± 0.05 intima/media ratio, p < 0.05).


CONCLUSIONS
Intramural delivery of bortezomib reduces neointimal formation, possibly via a mechanism involving upregulation of the p27 and downregulation of the NF-kappaB. Bortezomib therefore may be an alternative therapeutic approach for preventing restenosis.