Jabbour Mark N, Elder James B, Samuelson Christian G, Khashabi Shabnam, Hofman Florence M, Giannotta Steven L, Liu Charles Y
Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA.
Neurosurgery. 2009 Jan;64(1):139-46; discussion 146-8. doi: 10.1227/01.NEU.0000334417.56742.24.
To identify and characterize the phenotypic and functional differences of endothelial cells derived from cerebral arteriovenous malformations (AVM), as compared with endothelial cells derived from a normal brain.
Isolated AVM brain endothelial cells and control brain endothelial cells were evaluated immunohistochemically for expression of the endothelial cell markers von Willebrand factor and CD31, as well as angiogenic factors including vascular endothelial growth factor A, interleukin-8, and endothelin-1. Vascular endothelial growth factor receptors 1 and 2 were also evaluated using immunohistochemistry techniques. Functional assays evaluated cell proliferation, cytokine production, tubule formation, and cell migration using the modified Boyden chamber technique.
Endothelial cells derived from AVMs expressed high levels of vascular endothelial growth factor A and significantly overexpressed the vascular endothelial growth factor receptors 1 and 2 (P < 0.05), as compared with control endothelial cells. In addition, comparison to control brain endothelial cells demonstrated that AVM brain endothelial cells proliferated faster, migrated more quickly, and produced aberrant tubule-like structures.
Endothelial cells derived from cerebral AVMs are highly activated cells overexpressing proangiogenic growth factors and exhibiting abnormal functions consistent with highly activated endothelial cells.
与源自正常脑组织的内皮细胞相比，鉴定和表征源自脑动静脉畸形（AVM）的内皮细胞的表型和功能差异。
对分离出的AVM脑内皮细胞和对照脑内皮细胞进行免疫组织化学评估，以检测内皮细胞标志物血管性血友病因子和CD31的表达，以及包括血管内皮生长因子A、白细胞介素-8和内皮素-1在内的血管生成因子的表达。还使用免疫组织化学技术评估血管内皮生长因子受体1和2。功能测定使用改良的Boyden小室技术评估细胞增殖、细胞因子产生、小管形成和细胞迁移。
与对照内皮细胞相比，源自AVM的内皮细胞表达高水平的血管内皮生长因子A，并显著过度表达血管内皮生长因子受体1和2（P<0.05）。此外，与对照脑内皮细胞相比表明，AVM脑内皮细胞增殖更快、迁移更快，并产生异常的管状样结构。
源自脑AVM的内皮细胞是高度活化的细胞，过度表达促血管生成生长因子，并表现出与高度活化内皮细胞一致的异常功能。
