Angioneogenese in cerebralen Arteriovernösen Malformationen

Arteriovenöse Malformationen werden in der Literatur meistens als angeborene und statische Gefäßmissbildungen beschrieben. Neuere Arbeiten und Erkenntnisse legen jedoch eine dynamische Biologie dieser Malformationen nahe. Daher wurden in der vorliegenden Arbeit mit Hilfe der Immunhistochemie insge...

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Bibliographic Details
Main Author: Battenberg, Elmar
Contributors: Sure, U. (PD Dr. med.) (Thesis advisor)
Format: Dissertation
Language:German
Published: Philipps-Universität Marburg 2004
Operative Medizin
Subjects:
AVM
HIF
Online Access:PDF Full Text
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Table of Contents: 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. CONCLUSION: 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.