1Department of Neurosurgery, Zhongnan Hospital of Wuhan University; and.
2Brain Research Center, Zhongnan Hospital of Wuhan University, Wuhan, Hubei Province, China.
J Neurosurg. 2023 Jun 16;139(6):1705-1714. doi: 10.3171/2023.4.JNS23479. Print 2023 Dec 1.
Moyamoya disease (MMD) is a chronic steno-occlusive cerebrovascular disease and features the formation of hazy collateral vessels at the base of the brain. Angiopoietin (Ang)-1 and -2, their receptor Tie-2, and vascular endothelial growth factor (VEGF) that regulate angiogenesis might be important in MMD pathophysiology and postoperative collateral formation. The goal of this study was to determine whether levels of these angiogenic factors could predict collateralization in patients with MMD.
A total of 196 patients with MMD and 57 with atherosclerotic cerebrovascular disease serving as controls were enrolled. Ang-1, Ang-2, Tie-2, and VEGF mRNA levels were analyzed in middle cerebral artery (MCA) arterial wall specimens by using real-time quantitative polymerase chain reaction. MCA and peripheral plasma concentrations of Ang-1, Ang-2, soluble Tie-2 (sTie-2), and VEGF were examined by enzyme-linked immunosorbent assay. Cerebral arteriography was performed 6 months after bypass surgery to assess the postoperative collateralization.
In MCA specimens, patients with MMD exhibited higher expression levels of Ang-1 and Ang-2 but lowered VEGF expression. The patients with MMD had significantly higher concentrations of Ang-1 and Ang-2 but lower levels of VEGF in MCA plasma. Peripheral plasma concentrations of these growth factors were not changed. MCA and peripheral plasma sTie-2 levels were both reduced in patients with MMD. The 6-month follow-up showed that patients with good collateral formation had lower sTie-2 levels in both MCA and peripheral plasma. Furthermore, the Suzuki stage and peripheral plasma sTie-2 level were significantly correlated with good postoperative collateral formation on multivariate analysis.
Ang-1, Ang-2, Tie-2, and VEGF are involved in MMD pathogenesis. The peripheral plasma level of sTie-2 can differentiate MMD from atherosclerotic cerebrovascular disease and serve as a novel biomarker to predict postoperative collateral formation.
烟雾病（MMD）是一种慢性狭窄-闭塞性脑血管病，其特征是脑底出现模糊的侧支血管形成。血管生成素（Ang）-1 和 -2、其受体 Tie-2 和血管内皮生长因子（VEGF）在 MMD 病理生理学和术后侧支形成中可能很重要。本研究旨在确定这些血管生成因子的水平是否可以预测 MMD 患者的侧支形成情况。
共纳入 196 例 MMD 患者和 57 例动脉粥样硬化性脑血管病患者作为对照组。采用实时定量聚合酶链反应分析大脑中动脉（MCA）动脉壁标本中 Ang-1、Ang-2、Tie-2 和 VEGF mRNA 水平。通过酶联免疫吸附试验检测 MCA 和外周血浆中 Ang-1、Ang-2、可溶性 Tie-2（sTie-2）和 VEGF 的浓度。旁路手术后 6 个月行脑血管造影评估术后侧支循环情况。
在 MCA 标本中，MMD 患者的 Ang-1 和 Ang-2 表达水平较高，但 VEGF 表达水平降低。MMD 患者的 MCA 血浆中 Ang-1 和 Ang-2 浓度明显升高，而 VEGF 浓度较低。这些生长因子的外周血浆浓度没有改变。MMD 患者 MCA 和外周血浆 sTie-2 水平均降低。6 个月随访显示，侧支循环良好的患者 MCA 和外周血浆中的 sTie-2 水平均较低。此外，多因素分析显示，铃木分期和外周血浆 sTie-2 水平与术后良好侧支形成显著相关。
Ang-1、Ang-2、Tie-2 和 VEGF 参与了 MMD 的发病机制。外周血浆 sTie-2 水平可区分 MMD 与动脉粥样硬化性脑血管病，并可作为预测术后侧支形成的新型生物标志物。
