Department of Human Genetics, University of Würzburg, Würzburg, Germany.
Neurogenetics. 2011 Feb;12(1):83-6. doi: 10.1007/s10048-010-0261-6. Epub 2010 Sep 23.
Mutations in CCM1, CCM2, or CCM3 lead to cerebral cavernous malformations, one of the most common hereditary vascular diseases of the brain. Endothelial cells within these lesions are the main disease compartments. Here, we show that adenoviral CCM3 expression inhibits endothelial cell migration, proliferation, and tube formation while downregulation of endogenous CCM3 results in increased formation of tube-like structures. Adenoviral CCM3 expression does not induce apoptosis under normal endothelial cell culture conditions but protects endothelial cells from staurosporine-induced cell death. Tyrosine kinase activity profiling suggests that CCM3 supports PDPK-1/Akt-mediated endothelial cell quiescence and survival.
CCM1、CCM2 或 CCM3 的突变导致脑海绵状血管畸形，这是大脑最常见的遗传性血管疾病之一。这些病变中的内皮细胞是主要的疾病部位。在这里，我们表明腺病毒 CCM3 的表达抑制内皮细胞的迁移、增殖和管状结构的形成，而下调内源性 CCM3 则导致管状结构的形成增加。在正常的内皮细胞培养条件下，腺病毒 CCM3 的表达不会诱导细胞凋亡，但能保护内皮细胞免受 staurosporine 诱导的细胞死亡。酪氨酸激酶活性分析表明，CCM3 支持 PDPK-1/Akt 介导的内皮细胞静止和存活。
