Chronic subdural hematoma (CSDH) is an angiogenic disease that is involved with many inflammatory mediators. Tie2 is predominantly expressed in the embryonic endothelium and plays an important role in the maturation and stabilization of the vasculature. Angiopoietin (Ang)1 and Ang2 are well-known ligands of the Tie2 receptor. We examined the expression of Ang1 and Ang2 in CSDH fluid and the expression of Tie-2 receptor and components of the angiogenic signaling pathways in the outer membrane of CSDH. Twenty-five samples of CSDH fluid and eight samples of outer membrane of CSDH were included. The concentrations of Ang1 and Ang2 in the CSDH fluid were measured using enzyme-linked immunosorbent assay (ELISA) kits. The expression of Tie2, phosphoinositide 3-kinase (PI3K), protein kinase B (Akt) mechanistic target of rapamycin (mTOR), GβL, 70 kDa ribosomal protein S6 kinase (p70S6K), eukaryotic initiation factor 4E (eIF-4E), and β-actin was examined by a Western blot analysis. The expression of Tie2, Akt, and mTOR was also examined by immunohistochemistry. The concentration of Ang2 in CSDH fluid was significantly higher than that in the serum or cerebrospinal fluid (CSF), and also higher than that of Ang1 in CSDH fluid. Tie2, PI3K, Akt, mTOR, GβL, p70S6K, and eIF-4E were detected in all cases. In addition, Tie2, Akt, and mTOR were localized in the endothelial cells of vessels in the CSDH outer membrane. Our data suggest that Ang2, although not Ang1, in CSDH fluid promotes angiogenesis in endothelial cells through the Tie2 receptor. The Ang2/Tie2 signaling pathway might therefore be a useful therapeutic target for treating the growth of intractable CSDH.

中文翻译：

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血管生成素和血管生成信号通路分子在慢性硬膜下血肿中的表达。

慢性硬膜下血肿 (CSDH) 是一种血管生成性疾病，涉及许多炎症介质。Tie2 主要在胚胎内皮中表达，并在脉管系统的成熟和稳定中起重要作用。血管生成素 (Ang)1 和 Ang2 是众所周知的 Tie2 受体配体。我们检测了 Ang1 和 Ang2 在 CSDH 液中的表达以及 Tie-2 受体和 CSDH 外膜中血管生成信号通路组分的表达。包括25个CSDH液体样品和8个CSDH外膜样品。使用酶联免疫吸附测定 (ELISA) 试剂盒测量 CSDH 液中 Ang1 和 Ang2 的浓度。Tie2、磷酸肌醇 3-激酶 (PI3K)、雷帕霉素 (mTOR)、GβL、蛋白激酶 B (Akt) 机制靶标的表达 通过蛋白质印迹分析检查了 70 kDa 核糖体蛋白 S6 激酶 (p70S6K)、真核起始因子 4E (eIF-4E) 和 β-肌动蛋白。还通过免疫组织化学检查了 Tie2、Akt 和 mTOR 的表达。CSDH液中Ang2的浓度显着高于血清或脑脊液(CSF)，也高于CSDH液中的Ang1。在所有情况下均检测到 Tie2、PI3K、Akt、mTOR、GβL、p70S6K 和 eIF-4E。此外，Tie2、Akt 和 mTOR 定位于 CSDH 外膜血管的内皮细胞中。我们的数据表明，虽然不是 Ang1，但 CSDH 流体中的 Ang2 通过 Tie2 受体促进内皮细胞的血管生成。因此，Ang2/Tie2 信号通路可能是治疗难治性 CSDH 生长的有用治疗靶点。