Cellular loci involved in the pathogenesis of brain arteriovenous malformations

In this study, we will test our hypothesis that mutant endothelial cells impair mural function through a reduction of PDGFB expression, and activate microglia, astrocytes, and fibroblasts through endothelial inflammation; malfunction of other cells further enhances endothelial inflammation and bAVM severity. We will test (1) if mutant endothelial cells impair mural cell function through reduction of PDGFB expression and imbalance of EPHRINB2/EPHB4 signaling (2) if mutant endothelial cells activate microglia and astrocytes, and fibroblasts through endothelial inflammation. The goal of this study is to identify new targets for developing new therapies for bAVM patients.