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.
See, F., Watanabe, M., Kompa, A. R., Wang, B. H., Boyle, A., Kelly, D. J., Gilbert, R. E., & Krum, H. (2013). Early and delayed tranilast treatment reduces pathological fibrosis following myocardial infarction. Heart Lung and Circulation, 22(2), 122 - 132. https://doi.org/10.1016/j.hlc.2012.08.054