Article
Hypoxia inducible factor and vascular endothelial growth factor is expressed more frequently in embolized than in non-embolized cerebral arteriovenous malformations
HIF und VEGF werden häufiger in embolisierten als in nicht embolisierten AVMen exprimiert
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Published: | April 23, 2004 |
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Outline
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Objective
In previous studies, we documented a marked neoangiogenesis and endothelial proliferation in cerebral arteriovenous malfomations (AVMs) that were embolized prior to surgery when compared to those which were not embolized. We hypothesized that embolization causes a local hypoxia that promotes neoangiogenesis as a possible pathomechanism. To support this hypothesis, we now examine the angiogenesis-related proteins in a larger collective of patients. Additionally, we have investigated the hypoxia inducible factor-1 (HIF-1) as a possible protein operative during neoangiogenesis of cerebral AVMs.
Methods
The paraffin-embedded specimens of 56 AVMs obtained from surgical resection and 14 brain tissue controls were immunohistochemically stained with antibodies to PCNA, MIB-1, VEGF, Flk1 and HIF-1 by standard protocols.
Results
In AVMs treated with embolization prior to surgery (n=35, 63%), the expression of HIF-1 (p=0,0101) and VEGF (p=0,0007) was significantly higher (Fisher’s exact test) when compared to patients who did not have prior endovascular treatment. Differences in the expression of Flk-1 (p=0.0798) and PCNA (p=0,0423) were in the same direction, but 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 this data future animal studies need to be carried out.