Elucidating the contribution of SIAH2 to the development of cor pulmonale (B06)

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We have found that mice lacking the ubiquitin E3 ligase SIAH2 are largely protected from hypoxia-induced right heart hypertrophy. Against this background we will now investigate whether a time- and cardiomyocyte-specific deletion of Siah2 protects against right ventricular (RV) hypertrophy. We will also assess whether ongoing RVH can be inhibited or even reversed by inducible ablation of Siah2. The molecular targets, signaling pathways and metabolic changes regulated by SIAH2 in the right ventricle will be identified and further characterized. Additionally, we will test the applicability of SIAH2 inhibitors for the prevention and treatment of RV hypertrophy and failure.