Question: 

Apoptosis and hypertrophy are two actions that can be observed during the progress of heart failure. The transcription factor AP-1 is involved in both cardiac hypertrophy and apoptosis. In addition to AP-1, apoptosis requires SMAD proteins. The transcription factor YB-1 is able to interact with AP-1 as well as SMADs. Therefore, the question arises whether YB-1 is able to influence apoptosis and/or hypertrophy in adult cardiomyocytes and thus would counteract the development of heart failure.

Methods and Results: 

To answer this question we infected adult cardiomyocytes of rat with adenovirus overexpressing YB-1 (AdYB-1) and for control with adenovirus overexpressing GFP (AdGFP). AdYB-1 infection prevented TGFb-induced apoptosis. Expression analysis of SMAD4 showed significant increase after stimulation with TGFb. Similar results were obtained for JunD and JunB that build up the AP-1 dimer. Concomitant infection with AdYB-1 prevented increase in mRNA expression of SMAD4, JunD and JunB under TGFb. AdYB-1 overexpression also prevents a-adrenergic-induced hypertrophy with phenylephrine. The infection with AdYB-1 and PE induction of cardiomyocytes revealed a significant increase in RGS2 mRNA. The up-regulation of this cardiac Gq signalling inhibitor might prevent PE-induced hypertrophy.

Conclusion: 

We identified YB-1 as repressor for apoptosis and hypertrophy. Here YB-1 interferes both with SMAD and AP-1 signalling pathway and might be a perspective for a therapeutic target in heart failure.