| Blockade of TGF-β by catheter-based local intravascular gene delivery does not alter the in-stent neointimal response, but enhances inflammation in pig coronary arteries. | |
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MedLine Citation:
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PMID: 20053468 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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BACKGROUND: Extracellular matrix (ECM) accumulation significantly contributes to in-stent restenosis. In this regard, transforming growth factor (TGF)-β, a positive regulator of ECM deposition, may be implicated in in-stent restenosis. The goal of this study was to assess the effect of blockade of TGF-β on stent-induced restenosis in porcine coronary arteries. METHODS: An adenovirus expressing the ectodomain of the TGF-β type II receptor (AdTβ-ExR) was applied onto a coronary arterial segment of a pig (n=10) using an Infiltrator(TM), followed by stent deployment. Controls consisted of adenoviruses expressing β-galactosidase (AdLacZ) or phosphate-buffered saline (PBS) applied onto the other segment (n=10) of the same pig. RESULTS: Computer-based pathological morphometric analysis of stented coronary arteries, performed 4weeks after stenting, demonstrated no significant difference in morphometric parameters such as in-stent neointimal area and % area stenosis between the AdTβ-ExR group and control (n=7 for each). However the AdTβ-ExR group had increased neointimal cell density, infiltration of inflammatory cells mostly consisting of CD3(+) T cell, accumulation of hyaluronan, cell proliferation rate, and adventitial matrix metalloproteinase-1 (MMP-1) expression compared with control. The expression of connective tissue growth factor mRNA, measured by reverse transcription PCR, in cultured rat arterial smooth muscle cells was inhibited by AdTβ-ExR at moi 60. CONCLUSIONS: Blockade of TGF-β by catheter-based local intravascular gene delivery does not reduce stent-induced neointima formation 4weeks after stenting in spite of modest inhibition of ECM accumulation, but it induces vascular inflammation and associated pathological changes that may potentially aggravate lesion progression. |
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Authors:
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Ick-Mo Chung; Junwoo Kim; Youngmi K Pak; Yangsoo Jang; Woo-Ick Yang; Innoc Han; Seung-Jung Park; Seong-Wook Park; Jooryung Huh; Thomas N Wight; Hikaru Ueno |
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Publication Detail:
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Type: Journal Article Date: 2010-01-06 |
Journal Detail:
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Title: International journal of cardiology Volume: 145 ISSN: 1874-1754 ISO Abbreviation: Int. J. Cardiol. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-12-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8200291 Medline TA: Int J Cardiol Country: Netherlands |
Other Details:
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Languages: eng Pagination: 468-75 Citation Subset: IM |
Copyright Information:
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Copyright © 2009 Elsevier Ireland Ltd. All rights reserved. |
Affiliation:
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Division of Cardiology, Ewha Medical Research Institute, School of Medicine, Ewha Womans University, Seoul, Republic of Korea. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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