Increased angiopoietin2 expression is associated with endothelial apoptosis and blood-brain barrier breakdown
Increased angiopoietin2 expression is associated with endothelial apoptosis and blood-brain barrier breakdown
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DOI：
10.1038/labinvest.3700325
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发表时间：
2005-10-01
影响因子：
5
通讯作者：
Stewart, DJ
中科院分区：
文献类型：
--
作者：
Nag, S;Papneja, T;Stewart, DJ
正常脑内和软脑膜血管内皮细胞显示血管生成素（Ang）1的组成性表达，而微弱的Ang 2免疫反应性存在于偶尔的血管。在损伤后的早期阶段，损伤部位的血脑屏障（BBB）破坏与内皮Ang 1表达减少和Ang 2表达增加相关，这增加了Ang 2可能在早期BBB破坏中起作用的可能性。为了确定血管生成素2是否能引起血脑屏障的破坏，在正常大鼠皮层中研究了重组血管生成素2对脑血管对辣根过氧化物酶（HRP）通透性的影响。如所假设的，与媒介物注射的对照大鼠相比，Ang 2产生显著的BBB分解为HRP。由于Ang 2被报道具有促凋亡活性，Ang 2可能与内皮细胞凋亡相关的可能性在损伤后6小时至6天的大鼠皮质冷损伤模型中进行了研究。Caspase-3活性定位和TUNEL染色显示病变周围和软脑膜血管内皮细胞凋亡的证据。Ang蛋白和活性Caspase-3的双标记证实了Ang 2与活性Caspase-3的内皮共定位。这些数据表明，损伤后，Ang 2可能在损伤周围血管的BBB破坏中起作用，并且它也可能是损伤后第1天和第2天发生的内皮细胞凋亡的因素。
Normal intracerebral and pial vessels show constitutive expression of angiopoietin (Ang) 1 in endothelium while weak Ang2 immunoreactivity is present in occasional vessels. In the early phase postinjury, blood - brain barrier (BBB) breakdown at the lesion site is associated with decreased endothelial Ang1 and increased Ang2 expression, raising the possibility that Ang2 may have a role in early BBB breakdown. In order to determine whether Ang2 can cause BBB breakdown, the effect of recombinant Ang2 on cerebrovascular permeability to horseradish peroxidase (HRP) was studied in normal rat cortex. As hypothesized, Ang2 produced significant BBB breakdown to HRP as compared with vehicle-injected control rats. Since Ang2 is reported to have proapoptotic activity, the possibility that Ang2 may be associated with endothelial apoptosis was investigated in the rat cortical cold injury model over a period of 6 h to 6 days postinjury. Perilesion and pial vessels showed evidence of endothelial apoptosis as demonstrated by active Caspase-3 localization and TUNEL staining. Dual labeling for Ang proteins and active Caspase-3 demonstrated endothelial colocalization of Ang2 with active caspase-3. These data suggest that following injury, Ang2 may play a role in BBB breakdown of perilesional vessels, and it may also be a factor in endothelial cell apoptosis that occurs at days 1 and 2 following the injury.