Aims: 

Activin A (ActA) and myostatin (MSTN) are members of the transforming growth factor-b superfamily. They have negative effects on tissue growth, are expressed in myocardium and upregulated after myocardial infarction. Pathogenic mechanisms of dilated cardiomyopathy are not clearly understood. We studied the time course expression of cardiac MSTN and ActA systems together with markers of the apoptotic process in a canine model of tachycardiomyopathy.

Methods: 

Endomyocardial biopsies were weekly taken from 15 dogs during development (7 weeks) of tachycardiomyopathy. Cardiac gene expression of MSTN, ActA, their receptors and modulating ligands together with Bax, Bcl-2, caspases 9 and 3 were assessed by real-time quantification PCR.

Results: 

MSTN, activin receptor I, follistatin, activin receptor interacting protein 1, Bax, Bcl-2 and caspase 9 stayed unchanged. ActA increased with a four fold overexpression in overt heart failure (4.1 ± 1.6 wk 7 vs. 1 ± 0.2 wk 0). A 2 fold decrease of activin receptor IIA (0.6 ± 0.09 vs. 1 ± 0.12), IIB (0.5 ± 0.05 vs. 1 ± 0.09) and activin receptor interacting protein 2 (0.5 ± 0.09 vs. 1 ± 0.11) was observed. Caspase 3 increased (2.1 ± 0.37 vs. 1 ± 0.16) and was correlated with ActA, but, at immunohistochemistry, apoptototic nuclei were not increased compared to controls.

Conclusion: 

The activin system may play a role in the development of experimental dilated cardiomyopathy more than myostatin and pro-apoptotic signalling.