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内皮祖细胞诱导血管生成:脑硬脑膜动脉吻合术中新生血管形成的潜在机制

Endothelial Progenitor Cells Induce Angiogenesis: a Potential Mechanism Underlying Neovascularization in Encephaloduroarteriosynangiosis.

作者信息

Wang Qian-Nan, Zou Zheng-Xing, Wang Xiao-Peng, Zhang Qian, Zhao Ya-Qun, Duan Lian, Bao Xiang-Yang

机构信息

Department of Neurosurgery, The Eighth Medical Center of Chinese PLA General Hospital, Beijing, China.

Department of Neurosurgery, The Fifth Medical Center of Chinese PLA General Hospital, 8 Dong-Da Street, Fengtai District, Beijing, 100071, China.

出版信息

Transl Stroke Res. 2021 Apr;12(2):357-365. doi: 10.1007/s12975-020-00834-9. Epub 2020 Jul 6.

DOI:10.1007/s12975-020-00834-9
PMID:32632776
Abstract

Encephaloduroarteriosynangiosis (EDAS) is one of the most commonly used indirect vascular reconstruction methods. EDAS aids in the formation of collateral vessels from the extracranial to the intracranial circulation in patients with moyamoya disease (MMD). However, the underlying mechanism of collateral vessel formation is not well understood. Endothelial progenitor cells (EPCs) differentiate to form the vascular endothelial cells and play a very important role in angiogenesis. We designed this prospective clinical trial to investigate the presence of EPCs in patients with MMD and to explore the neovascularization mechanism mediated by the EPCs in EDAS. The patients who were diagnosed with MMD were recruited between February 5, 2017, and January 7, 2018. The blood samples were obtained from an antecubital vein and were analyzed using flow cytometry. EPCs were defined as CD34CD133CD45KDR. All the patients enrolled in the study underwent EDAS. Cerebral arteriography was performed 6 months post-EDAS to assess the efficacy of synangiosis. The correlation between EPC count and good collateral circulation was evaluated. Among the 116 patients with MMD enrolled in this study, 73 were women and 43 were men. The average age of the patients was 33.8 ± 15.2 years. The EPC count of the patients with MMD was 0.071% ± 0.050% (expressed as percentage of the peripheral blood mononuclear cells). The EPC count in the good postoperative collateral circulation group was significantly higher (0.085% ± 0.054%) than that in the poor collateral circulation group (0.048% ± 0.034%) (P = 0.000). The age, modified Suzuki-Mugikura grade, and EPC count were significantly correlated with the good collateral circulation post-EDAS in the multivariate analysis (P = 0.018, P = 0.007, and P = 0.003, respectively). The formation of collateral vessels by EDAS is primarily driven by angiogenesis. The EPC count may be the most critical factor for collateral circulation. The therapeutic effect of EDAS is more likely to benefit younger or severe ischemic patients with MMD.

摘要

脑-硬脑膜-动脉-血管融合术(EDAS)是最常用的间接血管重建方法之一。EDAS有助于烟雾病(MMD)患者形成从颅外到颅内循环的侧支血管。然而,侧支血管形成的潜在机制尚不完全清楚。内皮祖细胞(EPCs)分化形成血管内皮细胞,在血管生成中发挥非常重要的作用。我们设计了这项前瞻性临床试验,以研究MMD患者中EPCs的存在情况,并探讨EPCs在EDAS中介导的新生血管形成机制。2017年2月5日至2018年1月7日期间招募了确诊为MMD的患者。从前臂静脉采集血样,并用流式细胞术进行分析。EPCs被定义为CD34+CD133+CD45-KDR+。所有纳入研究的患者均接受了EDAS。EDAS术后6个月进行脑血管造影,以评估血管融合的疗效。评估了EPC计数与良好侧支循环之间的相关性。在本研究纳入的116例MMD患者中,女性73例,男性43例。患者的平均年龄为33.8±15.2岁。MMD患者的EPC计数为0.071%±0.050%(以外周血单个核细胞的百分比表示)。术后侧支循环良好组的EPC计数(分别为0.085%±0.054%)显著高于侧支循环不良组(0.048%±0.034%)(P = 0.000)。多因素分析显示,年龄、改良铃木-向仓分级和EPC计数与EDAS术后良好的侧支循环显著相关(分别为P = 0.018、P = 0.007和P = 0.003)。EDAS形成侧支血管主要由血管生成驱动。EPC计数可能是侧支循环的最关键因素。EDAS的治疗效果更可能使年轻或重度缺血的MMD患者受益。

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