Association of cardiotrophin-1 with myocardial fibrosis in hypertensive patients with heart failure
Cardiotrophin-1 has been shown to be profibrogenic in experimental models. The aim of this study was to analyze whether cardiotrophin-1 is associated with left ventricular end-diastolic stress and myocardial fibrosis in hypertensive patients with heart failure. Endomyocardial biopsies from patients...
| Autores: | , , , , , |
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| Formato: | artículo |
| Fecha de publicación: | 2014 |
| País: | España |
| Recursos: | Universidad de Navarra |
| Repositorio: | Dadun. Depósito Académico Digital de la Universidad de Navarra |
| Idioma: | inglés |
| OAI Identifier: | oai:dadun.unav.edu:10171/35967 |
| Acesso em linha: | https://hdl.handle.net/10171/35967 |
| Access Level: | acceso abierto |
| Palavra-chave: | Cardiotrophin I Collagen Fibrosis Heart failure |
| Resumo: | Cardiotrophin-1 has been shown to be profibrogenic in experimental models. The aim of this study was to analyze whether cardiotrophin-1 is associated with left ventricular end-diastolic stress and myocardial fibrosis in hypertensive patients with heart failure. Endomyocardial biopsies from patients (n=31) and necropsies from 7 control subjects were studied. Myocardial cardiotrophin-1 protein and mRNA and the fraction of myocardial volume occupied by collagen were increased in patients compared with controls ( P <0.001). Cardiotrophin-1 overexpression in patients was localized in cardiomyocytes. Cardiotrophin-1 protein was correlated with collagen type I and III mRNAs ( r =0.653, P <0.001; r =0.541, P <0.01) and proteins ( r =0.588, P <0.001; r =0.556, P <0.005) in all subjects and with left ventricular end-diastolic wall stress ( r =0.450; P <0.05) in patients. Plasma cardiotrophin-1 and N-terminal pro-brain natriuretic peptide and serum biomarkers of myocardial fibrosis (carboxy-terminal propeptide of procollagen type I and amino-terminal propeptide of procollagen type III) were increased ( P <0.001) in patients compared with controls. Plasma cardiotrophin-1 was correlated with N-terminal pro-brain natriuretic peptide ( r =0.386; P <0.005), carboxy- terminal propeptide of procollagen type I ( r =0.550; P <0.001), and amino-terminal propeptide of procollagen type III ( r =0.267; P <0.05) in all subjects. In vitro, cardiotrophin-1 stimulated the differentiation of human cardiac fibroblast to myofibroblasts ( P <0.05) and the expression of procollagen type I ( P <0.05) and III ( P <0.01) mRNAs. These findings show that an excess of cardiotrophin-1 is associated with increased collagen in the myocardium of hypertensive patients with heart failure. It is proposed that exaggerated cardiomyocyte production of cardiotrophin-1 in response to increased left ventricular end-diastolic stress may contribute to fibrosis through stimulation of fibroblasts in heart failure of hypertensive origin |
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