Neurosurgery Department, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
Neurosurgery Department, Yijishan Hospital, Wuhu 241001, Anhui Province, China.
Cytokine. 2018 Feb;102:123-130. doi: 10.1016/j.cyto.2017.07.020. Epub 2017 Sep 30.
Inflammation plays a crucial role in aneurysm wall remodeling, which could lead to the rupture of intracranial aneurysms. Stromal cell-derived factor 1α (SDF-1α), a vital inflammation cytokine, is also related to aneurysm pathogenesis. However, the characteristics of SDF-1α expression and its role in aneurysm remodeling remain largely unknown. In this study, we aimed to investigate the expression dynamics of SDF-1α and its correlation with aneurysm remodeling.
Saccular aneurysms were induced by porcine pancreatic elastase in New Zealand White rabbits. Aneurysm size was measured by digital subtraction angiography. Endothelial-like cells on the aneurysm wall were assessed on postoperative days 1, 3, 7, 14, 21, and 30. SDF-1α levels in the aneurysmal wall and serum were examined at several follow-up time points. Adherent molecule expression was examined, and migration assays were performed in vitro. After SDF-1α stimulation, the mobilization of endothelial-lineage cells and its role in the reendothelialization of the aneurysm wall were investigated in a saccular aneurysm rabbit model.
After the creation of saccular aneurysms in rabbits, the aneurysm sacs were filled with acute thrombosis within 3days, followed by a significant enlargement on day 14 and maturation on day 21. Serum SDF-1α levels increased in a bimodal fashion on day 1 and day 14, whereas SDF-1α expression in the aneurysm wall reached its maximum on day 14. VE-cadherin was up-regulated after SDF-1α stimulation and down-regulated by the SDF-1α ligand blocker AMD3100. Endothelial progenitor cell migration was enhanced by SDF-1α and blocked by AMD3100. The in vivo administration of SDF-α to rabbits with saccular aneurysms promoted endothelial-lineage cell mobilization into the peripheral blood and reendothelialization of the aneurysm wall.
The SDF-1α expression level in the peripheral blood and local aneurysm wall correlated with the aneurysm remodeling process in rabbits with elastase-induced saccular aneurysms. We conclude that SDF-1α may facilitate aneurysm wall remodeling by up-regulating VE-cadherin expression and mobilizing endothelial-lineage cells.
炎症在动脉瘤壁重塑中起着关键作用，这可能导致颅内动脉瘤破裂。基质细胞衍生因子 1α（SDF-1α）是一种重要的炎症细胞因子，也与动脉瘤的发病机制有关。然而，SDF-1α 的表达特征及其在动脉瘤重塑中的作用在很大程度上尚不清楚。本研究旨在探讨 SDF-1α 的表达动态及其与动脉瘤重塑的关系。
通过猪胰弹性蛋白酶诱导新西兰白兔形成囊状动脉瘤。通过数字减影血管造影术测量动脉瘤大小。术后第 1、3、7、14、21 和 30 天评估动脉瘤壁上的内皮样细胞。在多个随访时间点检测动脉瘤壁和血清中的 SDF-1α 水平。检测粘附分子的表达，并进行体外迁移实验。在兔囊状动脉瘤模型中，观察 SDF-1α 刺激后内皮谱系细胞的动员及其在动脉瘤壁再内皮化中的作用。
在兔形成囊状动脉瘤后，动脉瘤囊在 3 天内充满急性血栓，随后在第 14 天显著增大，第 21 天成熟。血清 SDF-1α 水平呈双峰式升高，第 1 天和第 14 天升高，而动脉瘤壁中 SDF-1α 的表达在第 14 天达到最高。SDF-1α 刺激后 VE-钙粘蛋白上调，SDF-1α 配体阻滞剂 AMD3100 下调。SDF-1α 增强内皮祖细胞迁移，AMD3100 阻断其迁移。将 SDF-α 体内给药于兔囊状动脉瘤可促进内皮谱系细胞动员至外周血，并促进动脉瘤壁的再内皮化。
弹性蛋白酶诱导的兔囊状动脉瘤中外周血和局部动脉瘤壁中的 SDF-1α 表达水平与动脉瘤重塑过程相关。我们的结论是，SDF-1α 可能通过上调 VE-钙粘蛋白的表达和动员内皮谱系细胞来促进动脉瘤壁重塑。
