title: Hypoxia-inducible factor and vascular endothelial growth factor are expressed more frequently in embolized than in nonembolized cerebral arteriovenous malformations.
abstract: OBJECTIVE
  In previous studies, we documented a marked neoangiogenesis and endothelial proliferation in cerebral arteriovenous malformations (AVMs) that were embolized before surgery compared with those that were not embolized. We hypothesized that embolization caused a local hypoxia that promotes neoangiogenesis as a possible pathomechanism. To support this hypothesis, we now examined the angiogenesis-related proteins in a larger cohort of patients. In addition, we investigated hypoxia-inducible factor-1 alpha as a possible protein operative during neoangiogenesis of cerebral AVMs.
  
  
  METHODS
  Paraffin-embedded specimens of 56 AVMs obtained from surgical resection and 14 brain tissue controls were immunohistochemically stained with antibodies to proliferating cell nuclear antigen, MIB-1, vascular endothelial growth factor, Flk1, and hypoxia-inducible factor-1 alpha by standard protocols.
  
  
  RESULTS
  In AVMs treated with embolization before surgery (n = 35, 63%), the expression of hypoxia-inducible factor-1 alpha (P = 0.0101) and vascular endothelial growth factor (P = 0.0007) was significantly higher (Fisher's exact test) than in patients who did not have previous endovascular treatment. Differences in the expression of Flk-1 (P = 0.0798) and proliferating cell nuclear antigen (P = 0.0423) were in the same direction but were not significant when corrected for multiple testing.
  
  
  CONCLUSIONS
  Our results provide circumstantial evidence that a partial occlusion of cerebral AVMs might induce local hypoxia-related neoangiogenesis. To support these data, future animal studies should be performed.
authors.affiliation: Neurochirurgische Klinik, Philipps-University, Marburg, Germany. sure@post.med.uni-marburg.de
authors.forename: Ulrich
authors.initials: U
authors.lastname: Sure
authors.forename: Elmar
authors.initials: E
authors.lastname: Battenberg
authors.forename: Astrid
authors.initials: A
authors.lastname: Dempfle
authors.forename: Wuttipong
authors.initials: W
authors.lastname: Tirakotai
authors.forename: Siegfried
authors.initials: S
authors.lastname: Bien
authors.forename: Helmut
authors.initials: H
authors.lastname: Bertalanffy
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001921:Brain / Q000098:blood supply / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000473:pathology / Q000601:surgery; D002648:Child; D003131:Combined Modality Therapy; D004621:Embolization, Therapeutic; D004730:Endothelium, Vascular / Q000473:pathology*; D005260:Female; D006801:Humans; D002534:Hypoxia, Brain / Q000473:pathology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D002538:Intracranial Arteriovenous Malformations / Q000473:pathology* / Q000601:surgery; D008297:Male; D008578:Meninges / Q000098:blood supply / Q000473:pathology; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000473:pathology* / Q000601:surgery; D011183:Postoperative Complications / Q000473:pathology*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D014157:Transcription Factors / Q000032:analysis*; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018809:Proliferating Cell Nuclear Antigen; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2