Abnormal pattern of Tie-2 and vascular endothelial growth factor receptor expression in human cerebral arteriovenous malformations
Abnormal pattern of Tie-2 and vascular endothelial growth factor receptor expression in human cerebral arteriovenous malformations
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DOI：
10.1097/00006123-200010000-00022
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发表时间：
2000-10-01
期刊：
影响因子：
4.8
通讯作者：
Young, WL
中科院分区：
文献类型：
--
作者：
Hashimoto, T;Emala, CW;Young, WL
目的：人类脑动静脉畸形（AVM）被推测是由异常血管生成引起的。血管内皮生长因子受体（VEGF-Rs）和Tie-2在血管发生和血管生成中起关键作用。我们假设AVM的异常血管表型可能与VEGF-Rs和Tie-2的异常表达有关。方法：我们使用免疫印迹法检测了AVM和正常脑组织中Tie-2、VEGF-R1和VEGF-R2的表达。为了评估活跃的血管重塑，我们还测定了内皮型一氧化氮合酶的表达。CD 31表达用于控制Tie-2、VECF-Rs和内皮型一氧化氮合酶的内皮细胞质量。结果：CD 31在AVM和正常脑组织中的表达程度相似（99 ± 29%vs100 ± 20%，mean ± standard error，P = 0.98）。与正常脑组织相比，所有AVM中的Tie-2表达均显着降低（16 +/- 9% vs 100 +/-37%，P = 0.04）。VEGF-R1表达在5例AVM中的4例中降低，但平均值之间的差异不显著（35 +/- 8% vs 100 +/-42%，P = 0.14）。与正常脑组织相比，所有AVM中VEGF-R2表达均降低（28 +/- 6% vs 100 +/-29%，P = 0.03）。AVM血管内皮型一氧化氮合酶（eNOS）的表达与正常脑组织无显著性差异（106 ± 42%vs100 ± 25%，P = 0.91）。结论：AVM血管中存在Tie-2和VECF-Rs的异常表达，二者可能参与了AVM的发病机制。
OBJECTIVE: Human cerebral arteriovenous malformations (AVMs) are speculated to result from abnormal angiogenesis. Vascular endothelial growth factor receptors (VEGF-Rs) and Tie-2 play critical roles in vasculogenesis and angiogenesis. We hypothesized that the abnormal vascular phenotype of AVMs may be associated with abnormal expression of VEGF-Rs and Tie-2.METHODS: We measured the expression of Tie-2, VEGF-R1, and VEGF-R2 in AVMs and normal brain tissue, using immunoblotting. To assess active vascular remodeling, we also measured endothelial nitric oxide synthase expression. CD31 expression was used to control for endothelial cell mass for Tie-2, VECF-Rs, and endothelial nitric oxide synthase. Immunoblotting data were presented as relative expression, using normal brain tissue values as 100%.RESULTS: CD31 was expressed to similar degrees in AVMs and normal brain tissue (99 +/- 29% versus 100 +/- 20%, mean +/- standard error, P = 0.98). Tie-2 expression was markedly decreased in all AVMs, compared with normal brain tissue (16 +/- 9% versus 100 +/- 37%, P = 0.04). VEGF-R1 expression was decreased in four of five AVMs, but the difference between the mean values was not significant (35 +/- 8% versus 100 +/- 42%, P = 0.14). VEGF-R2 expression was decreased in all AVMs, compared with normal brain tissue (28 +/- 6% versus 100 +/- 29%, P = 0.03). There was no difference in endothelial nitric oxide synthase expression between AVMs and normal brain tissue (106 +/- 42% versus 100 +/- 25%, P = 0.91).CONCLUSION: AVM vessels exhibited abnormal expression of Tie-2 and VECF-Rs, both of which may contribute to the pathogenesis of AVMs.