Stromal cell-derived factor-1 promoted angiogenesis and inflammatory cell infiltration in aneurysm walls.
Stromal cell-derived factor-1 promoted angiogenesis and inflammatory cell infiltration in aneurysm walls.
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DOI：
10.3171/2013.9.jns122074
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发表时间：
2014-01
影响因子：
4.1
通讯作者：
Scott EW
中科院分区：
文献类型：
--
作者：
Hoh BL;Hosaka K;Downes DP;Nowicki KW;Wilmer EN;Velat GJ;Scott EW
一小部分脑动脉瘤破裂，但一旦破裂，后果是毁灭性的。目前未破裂动脉瘤的治疗包括手术、血管内治疗或观察等待。如果对动脉瘤生长和破裂的生物学机制有更好的了解，就可以开发出一种新的药物来防止未破裂的动脉瘤破裂。破裂的脑动脉瘤以炎症介导的血管壁重塑为特征。我们研究了基质细胞衍生因子-1（SDF-1）在脑动脉瘤炎症介导的血管壁重塑中的作用。人类动脉瘤，小鼠颈动脉瘤和小鼠颅内动脉瘤进行了研究免疫组织化学。对来自发展颈动脉瘤或颅内动脉瘤的小鼠的血液进行流式细胞术分析。采用趋化性细胞迁移实验和毛细血管形成实验研究SDF-1对内皮细胞和巨噬细胞的作用。将抗SDF-1阻断抗体给予小鼠，并与对照（载体）给药小鼠比较其对颈动脉瘤壁和颅内动脉瘤发展的影响。人类动脉瘤、小鼠颈动脉瘤和小鼠颅内动脉瘤均表达SDF-1;患有颈动脉瘤或颅内动脉瘤的小鼠具有表达CXCR 4（SDF-1受体）的祖细胞增加（分别为P<0.01和P<0.001）。人类动脉瘤和小鼠颈动脉瘤在动脉瘤壁中具有内皮细胞、巨噬细胞和毛细血管;并且人类动脉瘤壁中毛细血管的存在与巨噬细胞的存在相关（P=0.01）。SDF-1促进内皮细胞和巨噬细胞迁移（P<0.01），促进毛细血管形成（P<0.001）。当给予小鼠抗SDF-1阻断抗体时，动脉瘤壁中的内皮细胞（P<0.05）、毛细血管（P<0.05）和细胞增殖（P<0.05）显著减少。给予抗SDF-1阻断抗体的小鼠发生颅内动脉瘤显著较少（33%对给予对照IgG的小鼠中的89%）（P<0.05）。这些数据表明SDF-1与动脉瘤壁中的血管生成和炎性细胞迁移和增殖相关，并且可能在颅内动脉瘤的发展中起作用。
A small percentage of cerebral aneurysms rupture, but when they do, the effects are devastating. Current management of unruptured aneurysms consist of surgery, endovascular treatment, or watchful waiting. If the biology of how aneurysms grow and rupture were better known, a novel drug could be developed to prevent unruptured aneurysms from rupturing. Ruptured cerebral aneurysms are characterized by inflammation-mediated wall remodeling. We studied the role of stromal cell-derived factor-1 (SDF-1) in inflammation-mediated wall remodeling in cerebral aneurysms. Human aneurysms; murine carotid aneurysms; and murine intracranial aneurysms were studied by immunohistochemistry. Flow cytometry analysis was performed on blood from mice developing carotid aneurysms or intracranial aneurysms. The effect of SDF-1 on endothelial cells and macrophages was studied by chemotaxis cell migration assay and capillary tube formation assay. Anti-SDF-1 blocking antibody was given to mice and compared to control (vehicle)-administered mice for its effects on the walls of carotid aneurysms and the development of intracranial aneurysms. Human aneurysms, murine carotid aneurysms, and murine intracranial aneurysms, all express SDF-1; and mice with developing carotid aneurysms or intracranial aneurysms have increased progenitor cells expressing CXCR4, the receptor for SDF-1 (P<0.01 and P<0.001, respectively). Human aneurysms and murine carotid aneurysms have endothelial cells, macrophages, and capillaries in the walls of the aneurysms; and the presence of capillaries in the walls of human aneurysms is associated with presence of macrophages (P=0.01). SDF-1 promotes endothelial cell and macrophage migration (P<0.01 for each), and promotes capillary tube formation (P<0.001). When mice are given anti-SDF-1 blocking antibody, there is a significant reduction in endothelial cells (P<0.05), capillaries (P<0.05), and cell proliferation (P<0.05) in the aneurysm wall. Mice given anti-SDF-1 blocking antibody develop significantly fewer intracranial aneurysms (33% versus 89% in mice given control IgG)(P<0.05). These data suggest SDF-1 associated with angiogenesis and inflammatory cell migration and proliferation in the walls of aneurysms, and may have a role in the development of intracranial aneurysms.