Early and delayed tranilast treatment reduces pathological fibrosis following myocardial infarction

Fiona See, Masataka Watanabe, Andrew Richard Kompa, Bing Hui Wang, Andrew Boyle, Darren James Kelly, Richard E Gilbert, Henry Krum

Research output: Contribution to journalArticleResearchpeer-review

18 Citations (Scopus)

Abstract

Background: Tranilast has been shown to inhibit TGF 1-related fibrosis and organ failure in various disease models. We sought to examine the effects of tranilast on left ventricular (LV) remodelling post-MI. Methods: Following coronary artery ligation, Sprague Dawley rats were randomised to receive tranilast (300 mg/kg/d, p.o.) or vehicle control over one of two treatment periods: (1) from 24 h until seven days post-MI, (2) from seven days to 28 days post-MI. Cardiac tissue was harvested for molecular, immunohistochemical and cell culture analyses. Results: Tranilast treatment of MI rats from 24 h until seven days post-MI reduced myocardial collagen content, 1 (I) procollagen, TGF 1 and CTGF mRNA transcripts, monocyte/macrophage infiltration and exacerbated infarct expansion compared with vehicle-treatment. Delaying the commencement of tranilast treatment to seven days post-MI attenuated myocardial fibrosis, gene expression of 1(I) procollagen, 1(III) procollagen, fibronectin, TGF 1 and CTGF mRNA transcripts, and monocyte/macrophage infiltration at 28d compared to vehicle-treatment, without detriment to infarct healing. Extended post-MI also preserved LV infarct size. In cultures of rat cardiac fibroblasts, tranilast attenuated TGF 1-stimulated fibrogenesis. Conclusion: Tranilast inhibits myocardial TGF 1 expression, fibrosis in rat post-MI and collagen production in cardiac fibroblasts. While tranilast intervention from 24 h post-MI exacerbated infarct expansion, delaying the commencement of treatment to seven days post-MI impeded LV remodelling.
Original languageEnglish
Pages (from-to)122 - 132
Number of pages11
JournalHeart Lung and Circulation
Volume22
Issue number2
DOIs
Publication statusPublished - 2013

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