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可以免受缺氧引起的右心肥大的影响。在此背景下，我们现在将研究 Siah2 的时间和心肌细胞特异性删除是否可以防止右心室 (RV) 肥大。我们还将评估 Siah2 的诱导消融是否可以抑制甚至逆转正在进行的 RVH。右心室中 SIAH2 调节的分子靶标、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 抑制剂预防和治疗 RV 肥大和衰竭的适用性。