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

阐明 SIAH2 对肺心病发生的贡献 (B06)

• 批准号: 314408762
• 金额: --
• 依托单位: Biochemisches Institut
• 依托单位国家: 德国
• 项目类别: Collaborative Research Centres
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/314408762?language=en
• 关键词: Elucidating; contribution; SIAH2; development; cor

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.

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厚的影响。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保护右心室（RV）肥厚。我们还将评估是否可以通过诱导消融Siah2来抑制甚至逆转正在进行的RVH。SIAH2在右心室中调控的分子靶点、信号通路和代谢变化将被确定并进一步表征。此外，我们将测试SIAH2抑制剂在预防和治疗右心室肥大和衰竭方面的适用性。