METHODS: Two remote coronary arterial segments (n=20) per pig randomly received 1x10(9) pfu of either AdT beta-ExR or adenovirus expressing beta-galactosidase (AdLacZ)/PBS, using an Infiltrator(TM). Stents (n=20) were deployed, after gene transfer, in each segment of 10 pigs. Localized transgene expression was confirmed by both reverse transcription-PCR and immunohistochemistry. Computer-based morphometric assessment was performed in the stented arteries 4 weeks after the gene transfer.

RESULTS: There was significantly less intimal area (1.57±0.49 vs. 2.13±0.34 mm2), area ratio of intima/media (0.84±0.44 vs. 1.32±0.48) and higher neointimal cell density (3121±330 vs. 2812±183 cells/mm2) in the arteries treated with AdT beta-ExR compared to the controls (all, p<0.05). Neither the cell proliferation rate, assessed by PCNA immunohistochemistry, nor the injury score were significantly different between the two groups. The distribution of hyaluronan in the intima was less in 4 of the 6 AdT beta-ExR treated arteries compared to the controls.

CONCLUSION: Blockade of TGF-beta, by a local in vivo gene transfer of a soluble TGF-beta receptor, inhibits stent-induced neointima, probably by inhibiting the ECM accumulation in porcine coronary arteries, which may have therapeutic potential in the inhibition of restenosis after stenting.