Stromal cell-derived factor 1a facilitates aneurysm remodeling in elastase-induced rabbit saccular aneurysm

Aims: Inflammation plays a crucial role in aneurysm wall remodeling, which could lead to the rupture of intracranial aneurysms. Stromal cell-derived factor la (SDF-1 alpha), a vital inflammation cytokine, is also related to aneurysm pathogenesis. However, the characteristics of SDF-1 alpha expression and its role in aneurysm remodeling remain largely unknown. In this study, we aimed to investigate the expression dynamics of SDF-1 alpha and its correlation with aneurysm remodeling. Methods: 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-1 alpha 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-1 alpha 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. Results: After the creation of saccular aneurysms in rabbits, the aneurysm sacs were filled with acute thrombosis within 3 days, followed by a significant enlargement on day 14 and maturation on day 21. Serum SDF-1 alpha levels increased in a bimodal fashion on day 1 and day 14, whereas SDF-1 alpha expression in the aneurysm wall reached its maximum on day 14. VE-cadherin was up-regulated after SDF-1 alpha stimulation and down-regulated by the SDF-1 alpha ligand blocker AMD3100. Endothelial progenitor cell migration was enhanced by SDF-1 alpha and blocked by AMD3100. The in vivo administration of SDF-alpha to rabbits with saccular aneurysms promoted endothelial-lineage cell mobilization into the peripheral blood and reendothelialization of the aneurysm wall. Conclusions: The SDF-1 alpha 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-1 alpha may facilitate aneurysm wall remodeling by up-regulating VE-cadherin expression and mobilizing endothelial lineage cells.