Recombinant human SDF-1α administration accelerates aneurysm neck reendothelialization in rabbit saccular aneurysm after flow diverter treatment

• 来源期刊: 生物化学与生物物理学报（英文版）
• 关键词: stromal cell-derived factor 1 neointima aneurysm flow diverter
• 年，卷（期）: 2017,（3）
• 页码范围: 246-253
• 页数: 8页
• 语种: 英文
• DOI: 10.1093/abbs/gmx001

摘要

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 into Escherichia 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 (50μg/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 of Tie-2,VE-cadherin,KDR and E-selectin were 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.