Artikel
Induction of vascular regrowth by incomplete embolization of cerebral AVMs
Inkomplette Embolisationen von AVMs induzieren vaskuläres Wachstum
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Autoren
Veröffentlicht: | 8. Mai 2006 |
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Gliederung
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Objective: A previous comparison between embolized and non-embolized cerebral arteriovenous malfomations (cAVMs) prior to surgery showed evidence of neoangiogenesis and endothelial proliferation. However, the mechanism occurring during growth or recurrence of an AVM is not completely understood. Our group hypothesized earlier that embolization causes a local hypoxia that promotes neoangiogenesis as a possible pathomechanism. To further support this hypothesis, we examined additional angiogenesis-related proteins in a large collective of cAVM patients. Results from hypoxia inducible factor-1α (HIF-1α) a possible protein operative during neoangiogenesis of cerebral AVMs were reviewed in all our previous studies.
Methods: The paraffin-embedded specimens of 58 AVMs obtained from surgical resection and 19 brain tissue controls were immunohistochemically stained with antibodies to PCNA, MIB-1, VEGF, bFGF, TGFα and HIF-1α by standard protocols.
Results: Endothelial positive immunostaining was observed in 84% of the cases for PCNA, in 43% for MIB-1, and in 80% for Flk-1 (receptor of vascular endothelial growth factor [VEGF]), respectively. Of 34 individuals treated with incomplete embolization prior to surgery, 22 (65%) showed an expression of VEGF, but only 3 of the 22 patients (14%) who were treated without prior embolization exhibited such an immunoreaction. The hypoxia inducible factor-1 (HIF-1α: plays a critical role in angiogenesis and stimulates the expression of VEGF) was expressed in 33/34 (97%) AVMs that were embolized prior to surgery, but only in 14/22 (64%) who did not undergo such preoperative treatment. Differences in the expression of Flk-1 and PCNA point in the same direction, but were not significant when corrected for multiple testing.
Conclusions: Our additional recent results for angiogenesis-related proteins support further evidence for local hypoxia related neoangiogenesis by partial interventional occlusion of cerebral AVMs. These results strongly maintain the hypothesis that AVMs have a growth potential, and that they are not of an embryological but of an acquired nature.