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Inhibition of Neointimal Formation after Stent Placement with Adenovirus-mediated Gene Transfer of IB in the Hypercholesterolemic Rabbit Model: Initial Results¹

¹ From the Departments of Radiology, Division of Angiography and Interventional Radiology (M.C., Z.X., M.G., J.L.) and Vascular Biology and Thrombosis Research (J.M.B., R.d.M., B.R.B.), the Center of Biomedical Research (H.B., U.L.), and Bone and Biomaterials Research, Institute for Histology and Embryology (H.P.), Vienna Medical School, Währinger Gürtel 18-20, A-1090 Vienna, Austria. Received June 6, 2001; revision requested July 20; final revision received November 9; accepted December 11. Supported in part by a Cardiovascular and Interventional Radiological Society of Europe research grant (1999), Mallinckrodt and Schering, and Boston Scientific. Address correspondence to M.C. (e-mail: manfred.cejna@univie.ac.at).

View larger version (79K): [in a new window]   Figure 1. a, Self-expandable nitinol stent, 15 mm long and 3.5 mm in diameter. b, Multichannel balloon, 3 mm in diameter and 20 mm long. Local application of a viral solution or PBS was performed at 6 atm at a balloon pressure of 3 atm, which displayed a jet- and weepinglike application of the fluid. c, Schematics depict the experimental setup for virus-treated or control animals.

View larger version (79K): [in a new window]   Figure 2. Representative photomicrographs of immunofluorescence-stained sections. a, PBS-treated control vessels do not express IB. IB is expressed primarily by smooth muscle cells of transfected vessel segments. b, IB transgene is expressed in a rabbit iliac artery 7 days after adenovirus-mediated gene transfer, as demonstrated with immunofluorescence detection of IB. Note the additional trauma in the dilated vessel areas treated with local drug delivery with partial disruption of the elastic membrane (arrowheads). The scale bar for a and b is 0.1 mm. c, On a photomicrograph, GFP transgene is expressed in rabbit liver 6 days after adenovirus-mediated gene transfer with immunofluorescence. (Original magnification, x100.)

View larger version (66K): [in a new window]   Figure 3. Representative photomicrographs of surface-stained ground sections. There is, as yet, no neointimal formation in the rabbit iliac artery with a stent on cross sections obtained 7 days after (a) stent placement alone or (b) gene transfer with IB. Only small cellular accumulations around the stent struts are seen in both samples (arrows). (van Giessen stain; original magnification, x40.)

View larger version (61K): [in a new window]   Figure 4. Photomicrographs of surface-stained ground sections obtained 4 weeks after stent implantation. a, Stent plus PBS treatment results in marked neointimal formation (arrows). b, Neointimal formation (arrows) is drastically reduced by the local delivery of rAdCMV.IB. The arrows delineate the extent of neointimal hyperplasia between the internal elastic lamina and the lumen in both samples. (van Giessen stain; original magnification, x40.)

View larger version (133K): [in a new window]   Figure 5. Representative digital subtraction angiograms at (a) 4 weeks after stent implantation alone, (b) stent plus PBS, and (c) stent plus IB treatment. The arrows indicate the proximal and distal borders of the stent.