Myostatin and IGF-I signaling in end-stage human heart failure: a qRT-PCR study

Journal of Translational Medicine

Luca Mendler⁴  Thomas Braun⁵  Péter Ferdinandy¹  László Dux³  Tamás Baranyai⁶  Mariusz Kuśmierczyk²  Przemyslaw Leszek²  Zoltán V Varga⁶  Júlia Aliz Baán³ 

[1] Pharmahungary Group, Szeged, Hungary;Institute of Cardiology, ul. Alpejska 42, Warszawa, 04-628, Poland;Department of Biochemistry, Faculty of General Medicine, University of Szeged, Dóm tér 9, Szeged, H-6720, Hungary;Institute of Biochemistry II, Goethe University, Faculty of Medicine, Theodor-Stern-Kai 7, Frankfurt, 60590, Germany;Department I - Cardiac Development and Remodelling, Max Planck Institute for Heart and Lung Research, Ludwigstrasse 43, Bad Nauheim, D-61231, Germany;Cardiometabolic Research Group, Department of Pharmacology and Pharmacotherapy, Semmelweis University, Nagyvárad tér 4, Budapest, H-1089, Hungary

关键词: miRNA;    microRNA-208;    qRT-PCR;    IGF-I receptor;    Activin receptor IIB;    IGF-I;    Myostatin;    Heart failure;   

Others  :  1146397
DOI  :  10.1186/s12967-014-0365-0

 received in 2014-09-22, accepted in 2014-12-16,  发布年份 2015

【 摘 要 】

Background

Myostatin (Mstn) is a key regulator of heart metabolism and cardiomyocyte growth interacting tightly with insulin-like growth factor I (IGF-I) under physiological conditions. The pathological role of Mstn has also been suggested since Mstn protein was shown to be upregulated in the myocardium of end-stage heart failure. However, no data are available about the regulation of gene expression of Mstn and IGF-I in different regions of healthy or pathologic human hearts, although they both might play a crucial role in the pathomechanism of heart failure.

Methods

In the present study, heart samples were collected from left ventricles, septum and right ventricles of control healthy individuals as well as from failing hearts of dilated (DCM) or ischemic cardiomyopathic (ICM) patients. A comprehensive qRT-PCR analysis of Mstn and IGF-I signaling was carried out by measuring expression of Mstn, its receptor Activin receptor IIB (ActRIIB), IGF-I, IGF-I receptor (IGF-IR), and the negative regulator of Mstn miR-208, respectively. Moreover, we combined the measured transcript levels and created complex parameters characterizing either Mstn- or IGF-I signaling in the different regions of healthy or failing hearts.

Results

We have found that in healthy control hearts, the ratio of Mstn/IGF-I signaling was significantly higher in the left ventricle/septum than in the right ventricle. Moreover, Mstn transcript levels were significantly upregulated in all heart regions of DCM but not ICM patients. However, the ratio of Mstn/IGF-I signaling remained increased in the left ventricle/septum compared to the right ventricle of DCM patients (similarly to the healthy hearts). In contrast, in ICM hearts significant transcript changes were detected mainly in IGF-I signaling. In paralell with these results miR-208 showed mild upregulation in the left ventricle of both DCM and ICM hearts.

Conclusions

This is the first demonstration of a spatial asymmetry in the expression pattern of Mstn/IGF-I in healthy hearts, which is likely to play a role in the different growth regulation of left vs. right ventricle. Moreover, we identified Mstn as a massively regulated gene in DCM but not in ICM as part of possible compensatory mechanisms in the failing heart.

【 授权许可】

   
2015 Baán et al.; licensee BioMed Central.

【 图 表 】

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