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

我们发现，缺乏泛素E3连接酶SIAH2的小鼠在很大程度上免受缺氧诱导的右心肥大。在此背景下，我们现在将研究Siah2的时间特异性和心肌细胞特异性缺失是否可以防止右心室（RV）肥大。我们还将评估是否可以通过Siah2的诱导性消融来抑制甚至逆转正在进行的RVH。SIAH2在右心室中调节的分子靶点、信号通路和代谢变化将被鉴定并进一步表征。此外，我们将测试SIAH2抑制剂用于预防和治疗RV肥大和衰竭的适用性。

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.