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

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

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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 InfiltratorTM, 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.

Original languageEnglish
Pages (from-to)468-475
Number of pages8
JournalInternational Journal of Cardiology
Volume145
Issue number3
DOIs
Publication statusPublished - 2010 Dec 3

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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