Expression of endothelial cell angiogenesis receptors in human cerebrovascular malformations
Expression of endothelial cell angiogenesis receptors in human cerebrovascular malformations
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DOI：
10.1097/00006123-200102000-00024
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发表时间：
2001-02-01
期刊：
影响因子：
4.8
通讯作者：
Awad, IA
中科院分区：
文献类型：
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作者：
Uranishi, R;Baev, NI;Awad, IA
目的：为了进一步了解血管生成因子在脑海绵状血管瘤（CCM）和动静脉畸形（AVM）发展中的作用，我们研究了手术切除病灶患者血管内皮生长因子（VEGF）和血管生成素系统受体的内皮细胞（EC）表达。方法：5个AVM、CCM和正常对照的石蜡包埋切片使用针对血管性血友病因子和 CD31（以表征 EC）以及血管生成生长因子受体 Flt-1 (VEGF-R1)、Flk-1 (VEGF-R2)、Tie-1 和 Tie-2 的抗体对脑组织样本进行免疫组织化学染色。我们对每个标本中的大小血管进行了计数，评估了每个标本对每种抗原的免疫表达，并分析了CCM、AVM和正常对照脑组织样本之间的差异。结果：CCM、AVM和正常对照脑组织样本的EC一致表达冯维勒布兰德因子，但CCM的EC大多呈CD31阴性（P < 0.05）。 Flk-1、Flt-1 和 Tie-2 在对照脑组织样本中不表达。 AVM 和 CCM 中 VEGF 受体 Flk-1 和 Flt-1 免疫阳性血管的比例显着高于对照脑组织样本（P < 0.05）。 AVM 和 CCM 中的 Tie-2 在免疫阳性血管中的表达比例高于对照脑组织样本，但差异不具有统计学意义。 Tie-1 在所有病变类型的稀有血管和对照脑组织样本中都有表达。结论：CCM 的 EC 似乎不像 AVM 和正常脑组织那样表达 CD31。与正常脑组织相比，AVM 和 CCM 表现出更高的 VEGF 受体表达，但血管生成素受体的表达不高。
OBJECTIVE: To further understand the role of angiogenic growth factors in the development of cerebral cavernous malformations (CCMs) and arteriovenous malformations (AVMs), we investigated endothelial cell (EC) expression of receptors for vascular endothelial growth factor (VEGF) and angiopoietin systems in patients with surgically resected lesions.METHODS: Paraffin-embedded sections of five AVMs, CCMs, and normal control brain tissue samples were stained immunohistochemically with antibodies to von Willebrand factor and CD31 (to characterize ECs) and angiogenesis growth factor receptors Flt-1 (VEGF-R1), Flk-1 (VEGF-R2), Tie-1, and Tie-2. We counted large and small vessels in each specimen, assessed each specimen's immunoexpression of each antigen, and analyzed differences between CCMs, AVMs, and the normal control brain tissue samples.RESULTS: The ECs of CCMs, AVMs, and normal control brain tissue samples expressed the von Willebrand factor uniformly, but the ECs of CCMs were largely negative for CD31 (P < 0.05). Flk-1, Flt-1, and Tie-2 were not expressed in the control brain tissue samples. The proportion of immunopositive vessels to VEGF receptors Flk-1 and Flt-1 was significantly greater in AVMs and CCMs than in the control brain tissue samples (P < 0.05). Tie-2 in AVMs and CCMs was expressed in a higher percentage of immunopositive vessels than in the control brain tissue samples, but the difference was not statistically significant. Tie-1 was expressed in rare vessels of all lesion types and control brain tissue samples.CONCLUSION: ECs of CCMs do not seem to express CD31 to the same extent that AVMs and normal brain tissue do. AVMs and CCMs show greater expression of VEGF receptors, but not of angiopoietin receptors, than normal brain tissue does.