Xu Ning, Meng Hao, Liu Tianyi, Feng Yingli, Qi Yuan, Zhang Donghuan, Wang Honglei
Department of Neurosurgery, The First Hospital of Jilin University, Changchun, China.
Front Physiol. 2019 Jan 8;9:1862. doi: 10.3389/fphys.2018.01862. eCollection 2018.
Stent-jailing and stent-jack are used for stent-assisted coil embolism (SCE) in intracranial aneurysm (IA) therapy, and cause different incidences of IA recurrence. Angiogenesis strongly correlates with aneurysm accumulation. Stent-jack causes higher mechanical forces in cerebral vessels than stent-jailing. Mechanical forces, as well as TGF-β/Smad2,3,4 signaling pathway, may play an important factor in IA recurrence by affecting angiogenesis. We explored the effects of stent-jailing or stent-jack technique on IA recurrence by investigating mechanical forces, TGF-β/Smad2,3,4 signaling pathway and the incidence of angiogenesis in IA patients. One-hundred-eighty-one IA patients were assigned into stent-jailing ( = 93) and stent-jacket groups ( = 88). The clinical outcome was evaluated using Glasgow Outcome Score (GOS) and aneurysm occlusion grades. The percentage of CD34EPCs (releasing pro-angiogenic cytokines) in peripheral blood was measured by flow cytometer. Endothelial cells were separated from cerebral aneurysm and malformed arteries via immunomagnetic cell sorting. Angiogenesis was measured by microvessel density (MVD) using anti-CD34 monoclonal antibody staining before using the stent, immediately after surgery and 2 years later. Meanwhile, the mechanical forces in cerebral vessels were determined by measuring endothelial shear stress (ESS) via a computational method. TGF-β and Smad2,3,4 were measured by real-time qPCR and Western Blot. Tube formation analysis was performed to test the relationship between angiogenesis and TGF-β, and the effects of different techniques on angiogenesis. After a 2-year follow-up, 85 and 81 patients from stent-jailing and stent-jack groups, respectively, completed the experiment. Stent-jailing technique improved GOS and reduced aneurysm occlusion grades higher than the stent-jack technique ( < 0.05). The counts of CD34EPCs and MVD values in the stent-jailing group were lower than the stent-jack group ( < 0.05). ESS values in sent-jailing group were lower than the stent-jack group ( < 0.05), and positively correlated with MVD values ( < 0.05). TGF-β and Smad2,3,4 levels in sent-jailing group were also lower than the stent-jack group ( < 0.05). TGF-β was associated with angiogenesis incidence and stent-jack caused angiogenesis incidence more than stent-jailing. Stent-jailing technique reduces IA recurrence more than stent-jack by causing less mechanical forces, angiogenesis and inhibiting TGF-β/Smad2,3,4 signaling in IA patients.
支架锚定术和支架撑开术用于颅内动脉瘤(IA)治疗中的支架辅助弹簧圈栓塞术(SCE),并导致不同的IA复发率。血管生成与动脉瘤形成密切相关。支架撑开术比支架锚定术在脑血管中产生更高的机械力。机械力以及TGF-β/Smad2、3、4信号通路可能通过影响血管生成在IA复发中起重要作用。我们通过研究IA患者的机械力、TGF-β/Smad2、3、4信号通路和血管生成发生率,探讨了支架锚定术或支架撑开术对IA复发的影响。181例IA患者被分为支架锚定术组(n = 93)和支架撑开术组(n = 88)。使用格拉斯哥预后评分(GOS)和动脉瘤闭塞分级评估临床结果。通过流式细胞仪测量外周血中CD34⁺内皮祖细胞(释放促血管生成细胞因子)的百分比。通过免疫磁珠细胞分选从脑动脉瘤和畸形动脉中分离内皮细胞。在使用支架前、手术后即刻和2年后,使用抗CD34单克隆抗体染色通过微血管密度(MVD)测量血管生成。同时,通过计算方法测量内皮剪切应力(ESS)来确定脑血管中的机械力。通过实时定量PCR和蛋白质免疫印迹法测量TGF-β和Smad2、3、4。进行管腔形成分析以测试血管生成与TGF-β之间的关系以及不同技术对血管生成的影响。经过2年随访,支架锚定术组和支架撑开术组分别有85例和81例患者完成实验。支架锚定术技术改善了GOS并降低了动脉瘤闭塞分级,优于支架撑开术技术(P < 0.05)。支架锚定术组中CD34⁺内皮祖细胞计数和MVD值低于支架撑开术组(P < 0.05)。支架锚定术组的ESS值低于支架撑开术组(P < 0.05),且与MVD值呈正相关(P < 0.05)。支架锚定术组中TGF-β和Smad2、3、4水平也低于支架撑开术组(P < 0.05)。TGF-β与血管生成发生率相关,且支架撑开术导致的血管生成发生率高于支架锚定术。支架锚定术技术通过在IA患者中产生较小的机械力、血管生成并抑制TGF-β/Smad2、3、4信号通路,比支架撑开术更能降低IA复发。