Recombinant human SDF-1alpha administration accelerates aneurysm neck reendothelialization in rabbit saccular aneurysm after flow diverter treatment.
Recombinant human SDF-1alpha administration accelerates aneurysm neck reendothelialization in rabbit saccular aneurysm after flow diverter treatment.
复制标题
重组人 SDF-1 α 给药可加速分流器治疗后兔囊状动脉瘤的动脉瘤颈再内皮化
DOI：
10.1093/abbs/gmx001
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发表时间：
2017
影响因子：
3.7
通讯作者：
Liu Jianmin
中科院分区：
文献类型：
--
作者：
Li Zifu;Zhao Rui;Fang Xinggen;Huang Qinghai;Liu Jianmin
动脉瘤瘤颈的再内皮化是血流导向装置（FD）植入后颅内动脉瘤血管修复的关键。重组人基质细胞衍生因子-1 α（rhSDF-1α）是干细胞的重要趋化因子，可促进内皮细胞的再内皮化。在这里，我们试图研究静脉注射rhSDF-1α的治疗效果，并揭示其促进动脉瘤颈再内皮化的潜在机制。重组质粒pET 32a-186转化大肠杆菌，获得具有生物学活性的rhSDF-1α蛋白。将FD植入新西兰白色兔弹性蛋白酶诱导的囊状动脉瘤中。FD植入后静脉注射rhSDF-1α（50 μg/kg/d），连续7 d。在这些手术后，在2或4周后收获动脉瘤。扫描电镜观察动脉瘤颈新生内膜厚度及内皮样细胞计数。4周后，检测动脉瘤颈新生内膜中内皮标记物的mRNA水平。迁移实验显示rhSDF-1α可诱导内皮祖细胞迁移，并呈剂量依赖性。支架植入后2周，随访血管造影显示每组各有1只动脉瘤部分闭塞，17只囊状动脉瘤兔（rhSDF-1α组9只，对照组8只）动脉瘤完全闭塞。动脉瘤颈新生内膜厚度无明显变化。有趣的是，rhSDF-1α组在2周（55 vs 13个细胞/高倍视野）和4周（104 vs 60个细胞/高倍视野）时在动脉瘤颈处观察到更多的内皮样细胞。Tie-2、VE-cadherin、KDR和E-selectin的mRNA表达水平较对照组显著升高。这些结果表明，静脉注射rhSDF-1α可加速FD植入后动脉瘤颈的再内皮化。我们的研究揭示了rhSDF-1α在诱导动脉瘤闭塞中的重要作用，并表明其通过调节再内皮化来实现其功能。
Reendothelialization in the aneurysm neck is pivotal to vascular repair for intracranial aneurysm after flow diverter (FD) implantation. Recombinant human stromal cell-derived factor 1α (rhSDF-1α) is a vital chemoattractant to stem cells and potentially facilitates reendothelialization. Here, we sought to investigate the therapeutic effects of intravenous administration of rhSDF-1α and uncover its potential mechanism for promoting aneurysm neck reendothelialization. Recombinant pET32a-186 plasmid was transformed intoEscherichia colito produce the rhSDF-1α protein with biological activity. FD was implanted into the elastase-induced saccular aneurysm in New Zealand white rabbits. rhSDF-1α (50 μg/kg/day) was intravenously administrated for consecutive 7 days after FD implantation. After these procedures, aneurysms were harvested after 2 or 4 weeks. Scanning electron microscopy was used to measure the neointima thickness and count the endothelial-like cells at aneurysm neck. Four weeks later, the mRNA levels of endothelial markers in the neointima at aneurysm neck were examined. Migration assay showed that rhSDF-1α could induce migration of endothelial progenitor cells in a dose-dependent manner. Two weeks after stent implantation, follow-up angiography showed partial aneurysm occlusion in one of each group and total aneurysm occlusion in 17 saccular aneurysm rabbits (9 of the rhSDF-1α group and 8 of the control group). No significant change of neointima thickness at aneurysm neck was observed. Intriguingly, more endothelial-like cells were observed at aneurysm neck in the rhSDF-1α group at 2 weeks (55 vs 13 cells per high-power field) and 4 weeks (104 vs 60 cells per high-power field). The mRNA levels ofTie-2,VE-cadherin,KDRandE-selectinwere significantly enhanced compared with those of the control group. These results showed that intravenous administration of rhSDF-1α can accelerate reendothelialization in the aneurysm neck after FD implantation. Our study reveals an important role of rhSDF-1α in inducing aneurysm occlusion and suggests that it achieves its function through modulating the reendothelialization.