Document Detail

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.
MedLine Citation:
PMID:  20053468     Owner:  NLM     Status:  MEDLINE    
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, 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 4 weeks 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 4 weeks 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.
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:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-01-06
Journal Detail:
Title:  International journal of cardiology     Volume:  145     ISSN:  1874-1754     ISO Abbreviation:  Int. J. Cardiol.     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-12-14     Completed Date:  2011-04-08     Revised Date:  2013-04-25    
Medline Journal Info:
Nlm Unique ID:  8200291     Medline TA:  Int J Cardiol     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  468-75     Citation Subset:  IM    
Copyright Information:
Copyright © 2009 Elsevier Ireland Ltd. All rights reserved.
Division of Cardiology, Ewha Medical Research Institute, School of Medicine, Ewha Womans University, Ewha Womans University Mokdong Hospital, Seoul, Republic of Korea.
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MeSH Terms
Antigens, CD3 / metabolism
Cells, Cultured
Connective Tissue Growth Factor / genetics
Coronary Artery Disease / therapy*
Gene Transfer Techniques*
Hyaluronic Acid / metabolism
Matrix Metalloproteinase 1 / metabolism
Muscle, Smooth, Vascular / cytology,  physiology
Neointima / therapy*
Protein-Serine-Threonine Kinases / genetics*
Rats, Sprague-Dawley
Receptors, Transforming Growth Factor beta / genetics*
Stents / adverse effects*
T-Lymphocytes / cytology
Transforming Growth Factor beta / antagonists & inhibitors*
Grant Support
HL 18645/HL/NHLBI NIH HHS; P01 HL018645/HL/NHLBI NIH HHS; P01 HL018645-320023/HL/NHLBI NIH HHS; P01 HL018645-330023/HL/NHLBI NIH HHS; P01 HL018645-340023/HL/NHLBI NIH HHS
Reg. No./Substance:
0/Antigens, CD3; 0/Ctgf protein, rat; 0/Receptors, Transforming Growth Factor beta; 0/Transforming Growth Factor beta; 139568-91-5/Connective Tissue Growth Factor; 9004-61-9/Hyaluronic Acid; EC Kinases; EC growth factor-beta type II receptor; EC Metalloproteinase 1

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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