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Journal of Translational Medicine

, 13:1

First Online: 16 January 2015Received: 22 September 2014Accepted: 16 December 2014DOI: 10.1186-s12967-014-0365-0

Cite this article as: Baán, J.A., Varga, Z.V., Leszek, P. et al. J Transl Med 2015 13: 1. doi:10.1186-s12967-014-0365-0

Abstract

BackgroundMyostatin 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.

MethodsIn 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.

ResultsWe 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.

ConclusionsThis 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.

KeywordsHeart failure Myostatin IGF-I Activin receptor IIB IGF-I receptor qRT-PCR microRNA-208 miRNA AbbreviationsMstnMyostatin

ActRIIBActivin receptor IIB

IGF-IInsulin-like growth factor I

IGF-IRInsulin-like growth factor I receptor

HPRTHypoxanthine guanine phosphorybosyl-transferase

DCMDilated cardiomyopathy

ICMIschemic cardiomyopathy

CONTControl

CMVCytomegalovirus

miRmicroRNA

NYHANew York Heart Association

PAPMean pulmonary artery pressure

PWPMean pulmonary wedge pressure

LVEDLeft ventricular end-diastolic diameter

LVSDLeft ventricular end-systolic diameter

PWPosterior wall thickness

IVSInterventricular septum thickness

LVEFLeft ventricular ejection fraction

ACEAngiotensin converting enzyme

PDEPhosphodiesterase

PGC1αPeroxisome proliferator-activated receptor-γ coactivator 1-α

Júlia Aliz Baán and Zoltán V Varga contributed equally to this work

Júlia Aliz Baán and Zoltán V Varga contributed equally to this work.

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Author: Júlia Aliz Baán - Zoltán V Varga - Przemyslaw Leszek - Mariusz Kuśmierczyk - Tamás Baranyai - László Dux - Péter 

Source: https://link.springer.com/







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