The extracellular matrix and the clonogenic survival benefit of CCM3-/- endothelial cells as new therapeutic targets for cerebral cavernous malformations

CCM3-/-内皮细胞的细胞外基质和克隆生存益处作为脑海绵状血管瘤新的治疗靶点

• 批准号: 383067719
• 负责人: Professor Dr. Matthias Rath
• 金额: --
• 依托单位: Institut für Humangenetik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/383067719?language=en
• 关键词: extracellular; matrix; clonogenic; survival; benefit

The recently identified clonogenic survival benefit of CCM3-/- endothelial cells has the potential to open up a new perspective on CCM pathogenesis. Since this effect of long-term CCM3 inactivation is still insufficiently understood, the project aims to clarify the molecular basis of apoptosis resistance of CCM3-deficient endothelial cells and to identify new drugs to inhibit this pathway. Thus, the project also intends to provide a better understanding of the regulation of angiogenesis and vascular remodeling. In vitro co-culture and innovative three-dimensional organoid models which mimic the in vivo situation will be established. These novel assays can be used for high-throughput testing of pharmacological agents and could contribute to shortening therapy development for vascular diseases. Additionally, the role of a novel candidate protein of the extracellular matrix will be addressed with these assays.

最近发现的CCM3-/-内皮细胞的克隆性生存益处有可能为CCM的发病机制开辟新的视角。由于CCM3长期失活的这种作用尚不清楚，该项目旨在阐明CCM3缺陷内皮细胞耐凋亡的分子基础，并寻找抑制这一途径的新药。因此，该项目还打算更好地了解血管生成和血管重塑的调节。将建立体外共培养和模拟体内情况的创新三维有机模型。这些新的检测方法可用于药物的高通量测试，并有助于缩短血管疾病的治疗开发。此外，一种新的细胞外基质候选蛋白的作用将通过这些检测得到解决。