Early and delayed tranilast treatment reduces pathological fibrosis following myocardial infarction.

Background: Tranilast has been shown to inhibit TGFβ1-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 (300mg/kg/d, p.o.) or vehicle control over one of two treatment periods: (1) from 24h 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 24h until seven days post-MI reduced myocardial collagen content, α1 (I) procollagen, TGFβ1 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 α1(I) procollagen, α1(III) procollagen, fibronectin, TGFβ1 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 TGFβ1-stimulated fibrogenesis.
Conclusion: Tranilast inhibits myocardial TGFβ1 expression, fibrosis in rat post-MI and collagen production in cardiac fibroblasts. While tranilast intervention from 24h post-MI exacerbated infarct expansion, delaying the commencement of treatment to seven days post-MI impeded LV remodelling.
(Copyright © 2012 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)