Early and delayed tranilast treatment reduces pathological fibrosis following myocardial infarction.
Heart Lung Circ
; 22(2): 122-32, 2013 Feb.
Article
em En
| MEDLINE
| ID: mdl-22986349
ABSTRACT
BACKGROUND:
Tranilast has been shown to inhibit TGFß1-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, TGFß1 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, TGFß1 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 TGFß1-stimulated fibrogenesis.CONCLUSION:
Tranilast inhibits myocardial TGFß1 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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Expressão Gênica
/
Anti-Inflamatórios não Esteroides
/
Remodelação Ventricular
/
Fator de Crescimento Transformador beta1
/
Ortoaminobenzoatos
/
Infarto do Miocárdio
/
Miocárdio
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Heart Lung Circ
Assunto da revista:
ANGIOLOGIA
/
CARDIOLOGIA
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
Austrália