title: Ephrin B2 and EphB4 selectively mark arterial and venous vessels in cerebral arteriovenous malformation.
abstract: OBJECTIVE
  Ephrin type B receptor 4 (EphB4, Eph receptor) selectively binds ephrin B2 (Eph ligand). EphB4/ephrin B2 is involved in embryonic vessel development, vascular remodelling and pathological vessel formation in adults (including tumour angiogenesis). Binding of vascular endothelial growth factor (VEGF)-A to the endothelial-specific receptor VEGF receptor-2 is the main extracellular signal triggering angiogenic response. Little is known about the role of EphB4/ephrin B2 during angiogenesis and arteriovenous plasticity in cerebral arteriovenous malformation (cAVM). This study investigated EphB4 and ephrin B2 expression in cAVM.
  
  
  METHODS
  Haemorrhagic (H-AVM) and nonhaemorrhagic (NH-AVM) specimens of AVM nidus, obtained after microsurgical cAVM resection, and normal superficial temporal artery (STA) specimens, were analysed retrospectively. VEGF-A, EphB4 and ephrin B2 expression were studied by immunohistochemistry and immunoblotting.
  
  
  RESULTS
  In cAVM (10 H-AVM; 10 NH-AVM), VEGF-A was immunocytochemically localized to endothelial cells; strong endothelial cell staining was found for EphB4 in veins and ephrin B2 in arteries. Normal STA (n = 10) did not express EphB4 or ephrin B2. EphB4 and ephrin B2 expression was greater in H-AVM than in NH-AVM.
  
  
  CONCLUSIONS
  Endothelial cells are more active in H-AVM than NH-AVM. EphB4 and ephrin B2 play important roles in neovascularization and arteriovenous differentiation/plasticity. These data provide new insights into the aetiology of cAVM and lay a foundation for further study. The notch pathway induced by VEGF-A may be a key signalling pathway in this process.
authors: Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
authors: Jie
authors: J
authors: Bai
authors: Ya-Jie
authors: YJ
authors: Wang
authors: Li
authors: L
authors: Liu
authors: Yuan-Li
authors: YL
authors: Zhao
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D042783:Endothelial Cells / Q000378:metabolism; D004730:Endothelium, Vascular / Q000473:pathology*; D036388:Ephrin-B2 / Q000096:biosynthesis / Q000378:metabolism*; D005260:Female; D006801:Humans; D002538:Intracranial Arteriovenous Malformations / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000473:pathology*; D011485:Protein Binding; D036224:Receptor, EphB4 / Q000096:biosynthesis / Q000378:metabolism*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000096:biosynthesis / Q000378:metabolism; D012189:Retrospective Studies; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000378:metabolism; D055815:Young Adult
chemical_list: D036388:Ephrin-B2; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D036224:Receptor, EphB4; D040262:Receptors, Vascular Endothelial Growth Factor
keywords: Cerebral arteriovenous malformation; EphB4; arteriovenous plasticity; ephrin B2