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.
Highlights
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
In the present qRT-PCR study we report that Mstn/IGF-I signaling differs in left ventricle (LV) versus right ventricle (RV) even in healthy hearts and shows significant differences in Dilated cardiomyopathy (DCM) versus ischemic cardiomyopathic (ICM) patients
In the RV we have revealed similar signaling ratio in both types of failing hearts (Figure 2A-C) the reason for that was an upregulation of Mstn signaling in DCM patients while a downregulation of IGF-I signaling in ICM heart samples
Summary
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. No data are available about the regulation of gene expression of Mstn and IGF-I in different regions of healthy or pathologic human hearts, they both might play a crucial role in the pathomechanism of heart failure. Myostatin (Mstn), the growth inhibitor of skeletal muscle [1], was shown to be expressed in the heart tissue [2] with controversial data about its role in myocardial physiology and pathophysiology. Given the different functional requirements LV and RV should cope with, and the markedly different development of these regions, one could assume that the gene expression pattern of Mstn and IGF-I signaling might show remarkable spatial differences under both physiological and pathological conditions. In the present qRT-PCR study we report that Mstn/IGF-I signaling differs in LV versus RV even in healthy hearts and shows significant differences in DCM versus ICM patients
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
