Department of Neurosurgery, University Hospital Zurich, Zurich, Switzerland.
Neurosurg Focus. 2010 Sep;29(3):E3. doi: 10.3171/2010.6.FOCUS10125.
Cerebral cavernous malformations (CCMs) are among the most prevalent cerebrovascular malformations, and endothelial cells seem to play a major role in the disease. However, the underlying mechanisms, including endothelial intercellular communication, have not yet been fully elucidated. In this article, the authors focus on the endothelial junction proteins CD31, VE-cadherin, and occludin as important factors for functional cell-cell contacts known as vascular adhesion molecules and adherence and tight junctions.
Thirteen human CCM specimens and 6 control tissue specimens were cryopreserved and examined for the presence of VE-cadherin, occludin, and CD31 by immunofluorescence staining. Protein quantification was performed by triplicate measurements using western blot analysis.
Immunofluorescent analyses of the CCM sections revealed a discontinuous pattern of dilated microvessels and capillaries as well as increased expression of occludin, VE-cadherin, and CD31 in the intima and in the enclosed parenchymal tissue compared with controls. Protein quantification confirmed these findings by showing upregulation of the levels of these proteins up to 2-6 times.
A protocol enabling the molecular and morphological examination of the intercellular contact proteins in human CCM was validated. The abnormal and discontinuous pattern in these endothelial cell-contact proteins compared with control tissue explains the loose intercellular junctions that are considered to be one of the causes of CCM-associated bleeding or transendothelial oozing of erythrocytes. Despite the small number of specimens, this study demonstrates for the first time a quantitative analysis of endothelial junction proteins in human CCM.
脑内海绵状血管畸形（CCM）是最常见的脑血管畸形之一，内皮细胞似乎在该疾病中起主要作用。然而，包括内皮细胞间通讯在内的潜在机制尚未完全阐明。本文作者重点研究了内皮连接蛋白 CD31、VE-钙黏蛋白和紧密连接蛋白-1（occludin），它们作为血管黏附分子和黏附及紧密连接的重要功能细胞-细胞连接因子。
将 13 个人类 CCM 标本和 6 个对照组织标本冷冻保存，并通过免疫荧光染色检测 VE-钙黏蛋白、occludin 和 CD31 的存在。通过 Western blot 分析进行三重复测量来进行蛋白定量。
CCM 切片的免疫荧光分析显示，与对照相比，扩张的微脉管和毛细血管呈现不连续的模式，内膜和封闭的实质组织中 occludin、VE-钙黏蛋白和 CD31 的表达增加。蛋白定量通过显示这些蛋白水平上调 2-6 倍证实了这些发现。
验证了一种能够对人类 CCM 细胞间连接蛋白进行分子和形态学检查的方案。与对照组织相比，这些内皮细胞连接蛋白的异常和不连续模式解释了细胞间连接的松弛，这被认为是 CCM 相关出血或红细胞跨内皮渗出的原因之一。尽管标本数量较少，但本研究首次对人类 CCM 中的内皮连接蛋白进行了定量分析。
