Blockade of TGF-ββββby Catheter-based Gene Transfer of a Soluble TGF-ββββType II Receptor Inhibits Neointima Formed after Stenting

Background: Enhanced extracellular matrix (ECM) accumulation is an important finding in coronary stentrestenotic tissue, in which TGF-β, implicated in ECM formation, is expressed abundantly. We assessed thehypothesis that blockade of TGF-βby the local delivery of an adenovirus expressing a soluble form of the TGF-βtype II receptor (AdTβ-ExR), inhibits stent-induced neointima in porcine coronary arteries. Methods: Tworemote coronary arterial segments (n=20) per pig randomly received 1×109 pfu of either AdTβ-ExR or adenovirusexpressing β-galactosidase (AdLacZ)/PBS, using an InfiltratorTM. Stents (n=20) were deployed, aftergene 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 stentedarteries 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±330vs. 2812±183 cells/mm2) in the arteries treated with AdTβ-ExR compared to the controls (all, p