Early and Delayed Tranilast Treatment Reduces Pathological Fibrosis Following Myocardial Infarction

Sep 19, 2012Heart, lung & circulation

Early and late tranilast treatment may reduce harmful heart scarring after a heart attack

AI simplified

Longevity & Aging on OpenScience ↗PubMed ↗DOI ↗

Abstract

Tranilast treatment from 24 hours to seven days post-myocardial infarction (MI) reduced myocardial collagen content and TGFβ1 mRNA transcripts.

Tranilast may inhibit TGFβ1-related fibrosis and organ failure in post-MI settings.
Treatment initiated from 24 hours post-MI led to increased infarct expansion despite reduced collagen and inflammatory markers.
Delaying tranilast treatment to seven days post-MI decreased myocardial fibrosis and inflammatory cell infiltration without harming infarct healing.
Tranilast may reduce collagen production in cardiac fibroblasts when stimulated by TGFβ1.

AI simplified

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.

Full Text

Full text is available at the source.

View full text (XML) ↗View full text ↗

Early and Delayed Tranilast Treatment Reduces Pathological Fibrosis Following Myocardial Infarction

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the longevity & aging brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the longevity & aging brief