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

最近发现的CCM 3-/-内皮细胞的克隆存活益处有可能为CCM发病机制开辟新的视角。由于这种长期CCM 3失活的影响仍然没有得到充分的理解，该项目旨在阐明CCM 3缺陷内皮细胞抗凋亡的分子基础，并确定抑制该途径的新药。因此，该项目还旨在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类器官模型。这些新的检测方法可用于药物的高通量检测，并有助于缩短血管疾病的治疗开发。此外，一种新的候选蛋白质的细胞外基质的作用将解决这些测定。

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.