Human brain arteriovenous malformations express lymphatic-associated genes

摘要: Objective Brain arteriovenous malformations (AVMs) are devastating, hemorrhage-prone, cerebrovascular lesions characterized by well-defined feeding arteries, draining vein(s) and the absence of a capillary bed. The endothelial cells (ECs) that comprise AVMs exhibit loss arterial venous specification. Given role transcription factor COUP-TFII in vascular development, EC specification, pathological angiogenesis, we examined human AVM tissue to determine if COUP-FTII may have disease biology. Methods We 40 brain immunohistochemistry (IHC) qRT-PCR for expression as well other genes involved lymphatic maintenance, signaling. We also proliferation tube formation with umbilical ECs (HUVEC) following overexpression. Results We report expressed COUP-TFII, SOX18, PROX1, NFATC1, FOXC2, TBX1, LYVE1, Podoplanin, growth (VEGF)-C, contained Ki67-positive heterogeneously Hedgehog, Notch, Wnt, VEGF signaling pathways. Overexpression alone vitro resulted increased dilated tubes an assay HUVEC. Interpretation This suggests further losing their arterial/venous specificity acquiring partial molecular phenotype. There was significant correlation gene presence clinical edema acute hemorrhage. While precise these formation, stabilization, risk hemorrhage remains unclear, findings potentially important implications patient management treatment choice, opens new avenues future work on mechanisms.