TGFb1 is upregulated in the heart by increased work load and has been shown to be involved in hypertrophic growth as well as in apoptosis in cardiomyocytes. Since there is evidence for enhanced activity of other TGFb superfamily members under pathophysiological conditions in the heart. we now tested in this study if other TGFb superfamily members also induce apoptosis in ventricular cardiomyocytes of rat. Cardiomyocytes were stimulated with TGFb1 (1 ng/ml), myostatin (10 ng/ml), BMP2 (80 ng/ml), activin (100 ng/ml) and GDF15 (3 ng/ml). Apoptosis was induced by TGFb1, myostatin, activin A and BMP-2. In EMSAs we now could demonstrate that AP-1 and SMAD binding is activated by TGFb1, myostatin, BMP-2. Intracellular scavenging of SMAD or AP-1 binding activity by transformation of cardiomyocytes with SMAD-decoy oligos or AP-1 decoy oligos inhibited apoptosis induction by TGFb1, myostatin, BMP-2, and activin A. GDF15 shows anti-apoptotic effects. It inhibited the TGFb1 induced apoptosis. Conclusions: Most of the investigated TGFb-superfamily members activate the transcription factors AP-1 and SMAD and induce apoptosis in cardiomyocytes. GDF 15 has anti-apoptotic effects and inhibited the apoptotic effect of TGFb1.