alexa Stent-based delivery of tissue inhibitor of metalloproteinase-3 adenovirus inhibits neointimal formation in porcine coronary arteries.

Author(s): Johnson TW, Wu YX, Herdeg C, Baumbach A, Newby AC,

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Abstract BACKGROUND: Stent-based antiproliferative therapy appears to decrease in-stent restenosis. However, alternative approaches might produce equivalent efficacy with better long-term safety. In previous work, an adenovirus capable of expressing the tissue inhibitor of metalloproteinase-3 (RAdTIMP-3) inhibited neointima formation in cell cultures and porcine saphenous vein grafts. RAdTIMP-3 decreased smooth muscle cell migration, stabilized the extracellular matrix, and uniquely promoted apoptosis. The current study developed eluting stent technology to deliver RAdTIMP-3 during stenting of pig coronary arteries. METHODS AND RESULTS: Binding of virus to and elution from stents and transduction of pig coronary arteries were confirmed using beta-galactosidase as a reporter gene in vitro and in vivo. Deployment of RAdTIMP-3-coated stents increased apoptosis and reduced neointimal cell density, but did not increase inflammation or proliferation compared with beta-galactosidase-expressing adenovirus (RAdlacZ). Neointimal area after 28 days was significantly reduced to 1.27+/-0.19 mm2 with RAdTIMP-3 versus 2.61+/-0.31 mm2 with RAdlacZ stents (P<0.001) and 2.12+/-0.20 mm2 with bare stents (P<0.005). CONCLUSIONS: Our results demonstrate for the first time to our knowledge the feasibility of adenovirus-coated stent technology and highlight the potential of TIMP-3 to produce significant inhibition of in-stent neointima formation. This article was published in Arterioscler Thromb Vasc Biol and referenced in

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