Apoptosis is involved in transition from compensated cardiac hypertrophy to heart failure which is accompanied by an induction of TGFb/SMAD signalling pathway. The use of effective SMAD inhibitors may protect the heart against heart failure progression. The transcription factor YB-1 mediates inhibitory effects on genes associated with cell death and interacts with SMADs and AP-1. The question arises whether overexpression of YB-1 can influence TGFb induced apoptosis and how hypertrophy is affected by YB-1. Therefore, we infected isolated cardiomyocytes (CM) with an adenovirus (AdYB-1) and analyzed the effect of YB-1 on apoptosis and hypertrophy induction in these cells. TGFb₁ induced apoptosis while overexpression of YB-1 prevented this induction. After stimulation with a-adrenoceptoragonist phenylephrine (PE) a significant enlargement of cell cross sectional area and rate of protein synthesis was observed in non-infected CM. Infection of CM with AdYB-1 blocked the PE-induced hypertrophy. The hypertrophic stimulus GDF-15 also induced a significant enlargement of cell cross sectional area and rate of protein synthesis in non-infected CM. In contrast to PE-induced hypertrophy, AdYB-1 did not block GDF-15-induced hypertrophy.

Conclusion: 

We identified YB1 as a repressor of apoptosis and a-adrenergic hypertrophy in CM. YB-1 did not influence GDF-15-induced hypertrophy in CM. YB-1 therefore enables selective intervention in apoptotic and hypertrophic events.