He Jin, Wang Rong, Zhang Dong, Zhang Yan, Zhang Qian, Zhao Jizong
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, P.R. China.
Exp Ther Med. 2014 Jul;8(1):302-308. doi: 10.3892/etm.2014.1713. Epub 2014 May 14.
The aim of the present study was to investigate the levels of vascular endothelial growth factor (VEGF)-antagonizing cytokines and VEGF-influenced vascular stabilizing cytokines in patients with moyamoya disease (MMD) and the association with postoperative collateral vessel formation. The study population included 53 MMD patients that had undergone indirect bypass surgery and 50 healthy controls. Serum levels of VEGF, thrombospondin-1 (TSP-1), TSP-2, soluble VEGF receptor-1 (sVEGFR-1), sVEGFR-2, endostatin, angiopoietin-1 (Ang-1) and Ang-2 were measured at the baseline (preoperative) and at day seven following surgery. Postoperative collateralization assessment was conducted upon the six-month follow-up cerebral angiography. Cytokine levels were compared between patients with good or poor collateral formation. Compared with the healthy controls, MMD patients exhibited lower baseline levels of sVEGFR-1 (P<0.0001) and sVEGFR-2 (P<0.0001), but higher VEGF expression (P<0.0001). Ang-1 and Ang-2 levels did not exhibit any difference between the two groups. On day seven following surgery, MMD patients exhibited an almost unchanged sVEGFR-1 and sVEGFR-2 expression level, but upregulated expression of VEGF (P<0.0001), Ang-1 (P<0.0001) and TSP-2 (P<0.0001). The six-month follow-up angiographies revealed that 21 patients (45.65%) that had undergone the same surgical procedure achieved good collateralization. Patients with good collateral formation appeared to have lower sVEGFR-1 and sVEGFR-2 levels prior to (P=0.029 and P=0.045, respectively) and at day seven (P=0.044 and P=0.047, respectively) following bypass surgery when compared with the patients with worse collateralization. Therefore, sVEGFR-1 and sVEGFR-2 may play a role in the pathogenesis of MMD. Lower levels of sVEGFR-1 and sVEGFR-2 indicated better postoperative collateralization in the six months following indirect bypass surgery. However, Ang-1 and Ang-2 may not be specifically involved in the course of MMD.
本研究的目的是调查烟雾病（MMD）患者中血管内皮生长因子（VEGF）拮抗细胞因子和VEGF影响的血管稳定细胞因子的水平，以及与术后侧支血管形成的相关性。研究人群包括53例接受间接搭桥手术的MMD患者和50例健康对照者。在基线（术前）和术后第7天测量血清VEGF、血小板反应蛋白-1（TSP-1）、TSP-2、可溶性VEGF受体-1（sVEGFR-1）、sVEGFR-2、内皮抑素、血管生成素-1（Ang-1）和Ang-2的水平。在术后6个月的脑血管造影时进行术后侧支循环评估。比较侧支形成良好或不良患者的细胞因子水平。与健康对照者相比，MMD患者的sVEGFR-1（P<0.0001）和sVEGFR-2（P<0.0001）基线水平较低，但VEGF表达较高（P<0.0001）。两组之间的Ang-1和Ang-2水平没有差异。术后第7天，MMD患者的sVEGFR-1和sVEGFR-2表达水平几乎没有变化，但VEGF（P<0.0001）、Ang-1（P<0.0001）和TSP-2（P<0.0001）的表达上调。术后6个月的血管造影显示，21例（45.65%）接受相同手术的患者侧支循环良好。与侧支循环较差的患者相比，侧支形成良好的患者在搭桥手术前（分别为P=0.029和P=0.045）和术后第7天（分别为P=0.044和P=0.047）的sVEGFR-1和sVEGFR-2水平似乎较低。因此，sVEGFR-1和sVEGFR-2可能在MMD的发病机制中起作用。较低的sVEGFR-1和sVEGFR-2水平表明间接搭桥手术后6个月的术后侧支循环较好。然而，Ang-1和Ang-2可能未特别参与MMD的病程。
