Stent-Based Delivery of Tissue Inhibitor of Metalloproteinase-3 Adenovirus Inhibits Neointimal Formation in Porcine Coronary Arteries
- 1 April 2005
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Arteriosclerosis, Thrombosis, and Vascular Biology
- Vol. 25 (4), 754-759
- https://doi.org/10.1161/01.atv.0000157582.33180.a9
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 β-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 β-galactosidase–expressing adenovirus (RAd lac Z). Neointimal area after 28 days was significantly reduced to 1.27±0.19 mm 2 with RAdTIMP-3 versus 2.61±0.31 mm 2 with RAd lac Z stents ( P 2 with bare stents ( P 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.Keywords
This publication has 18 references indexed in Scilit:
- Carotid Intima-Media Thickness Is Associated With Premature Parental Coronary Heart DiseaseCirculation, 2003
- Relationship between type IV collagen degradation, metalloproteinase activity and smooth muscle cell migration and proliferation in cultured human saphenous veinCardiovascular Research, 2003
- Sirolimus-Eluting Stent Implanted in Human Coronary Artery for 16 MonthsCirculation, 2003
- Gene Delivery to Pig Coronary Arteries from Stents Carrying Antibody-Tethered AdenovirusHuman Gene Therapy, 2002
- Multicenter evaluation of the phosphorylcholinecoated biodivYsio stent in short de novo coronary lesions: The SOPHOS studyInternational Journal of Cardiovascular Interventions, 2000
- Gene transfer of tissue inhibitor of metalloproteinase-2 inhibits metalloproteinase activity and neointima formation in human saphenous veinsGene Therapy, 1998
- Adenovirus-Mediated Gene Transfer of the Human TIMP-1 Gene Inhibits Smooth Muscle Cell Migration and Neointimal Formation in Human Saphenous VeinHuman Gene Therapy, 1998
- Divergent effects of tissue inhibitor of metalloproteinase-1, -2, or -3 overexpression on rat vascular smooth muscle cell invasion, proliferation, and death in vitro. TIMP-3 promotes apoptosis.JCI Insight, 1998
- Adenovirus-mediated gene transfer into normal rabbit arteries results in prolonged vascular cell activation, inflammation, and neointimal hyperplasia.JCI Insight, 1995
- Biomembrnanes as models for polymer surfacesBiomaterials, 1986