doi: 10.1161/hc0502.102966
(Circulation. 2002;105:633.)
© 2002 American Heart Association, Inc.
Basic Science Reports |
Activation of Nuclear Factor-
B Significantly Contributes to Lumen Loss in a Rabbit Iliac Artery Balloon Angioplasty Model
From the Department of Vascular Biology and Thrombosis Research (J.M.B., A.K., G.B., S.S., Y.K., J.L., R.D.M., B.R.B.); Division of Angiography and Interventional Radiology (M.C., Z.X., J.L.), Department of Radiology; and Department of Biomedical Research (H.B., U.L.), University of Vienna, Austria.
Correspondence to Bernd R. Binder, Department of Vascular Biology and Thrombosis Research, University of Vienna, Schwarzspanierstrasse 17, A-1090 Vienna, Austria. E-mail bernd.binder{at}univie.ac.at
Background— To investigate the contribution of inflammation to postangioplasty lumen loss, we used an adenoviral gene therapy approach to inhibit the central inflammatory mediator nuclear factor-
B (NF-B) by overexpression of its natural inhibitor, IB
.
Methods and Results— The adenovirus carrying human IB was applied immediately after balloon dilatation by a double-balloon catheter in a rabbit iliac artery restenosis model. Immunohistochemistry of IB revealed that mainly smooth muscle cells of the media but also cells of the adventitia were transduced and expressed the transgene IB for 
8 days. At this time point, intercellular adhesion molecule-1 (30%) and monocyte chemotactic protein-1 (50%) expression, as well as recruitment of macrophages into the wounded area (90%), were significantly reduced in IB-treated vessels. In addition, expression of inhibitor of apoptosis proteins was reduced and the percentage of apoptotic cells was increased compared with control-treated contralateral vessels. Animals killed 5 weeks after treatment exhibited a significantly reduced degree of lumen narrowing (P<0.02) on the side treated with adenovirus IB. The lumen gain of 
40% was due to positive remodeling.
Conclusions— From these data, we conclude that balloon angioplasty–induced activation of NF-B contributes to lumen loss likely via induction of an inflammatory response and a decrease in the rate of apoptosis. These data show for the first time that inflammation mediated by NF-B is involved in postangioplasty lumen narrowing. Specific and more potent inhibitors of NF-B might therefore be a useful therapeutic measure to improve clinical outcome after balloon dilatation.
Key Words: restenosis • inflammation • gene therapy • nuclear factor-B • apoptosis
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