Erythropoietin Stimulates Endothelial Progenitor Cells to Induce Endothelialization in an Aneurysm Neck After Coil Embolization by Modulating Vascular Endothelial Growth Factor

Abstract

This study explored a new approach to enhance aneurysm (AN) neck endothelialization via erythropoietin (EPO)‐induced endothelial progenitor cell (EPC) stimulation. Results suggest that EPO enhanced the endothelialization of a coiled embolization AN neck by stimulating EPCs via vascular endothelial growth factor modulation. Thus, the promotion of endothelialization with EPO provides an additional therapeutic option for preventing the recurrence of ANs. Endovascular coil embolization is an attractive therapy for cerebral ANs, but recurrence is a main problem affecting long‐term outcomes. In this study, we explored a new approach to enhance AN neck endothelialization via EPO‐induced EPC stimulation. Ninety adult male Sprague‐Dawley rats were selected for an in vivo assay, and 60 of them underwent microsurgery to create a coiled embolization AN model. The animals were treated with EPO, and endothelial repair was assessed via flow cytometry, immunofluorescence, electronic microscopy, cytokine detection, and routine blood work. EPO improved the viability, migration, cytokine modulation, and gene expression of bone marrow‐derived EPCs and the results showed that EPO increased the number of circulating EPCs and improved endothelialization compared with untreated rats (p < .05). EPO had no significant effect on the routine blood work parameters. In addition, the immunofluorescence analysis showed that the number of KDR+ cells in the AN neck was elevated in the EPO‐treated group (p < .05). Further study demonstrated that EPO promoted EPC viability and migration in vitro. The effects of EPO may be attributed to the modulation of vascular endothelial growth factor (VEGF). In particular, EPO enhanced the endothelialization of a coiled embolization AN neck by stimulating EPCs via VEGF modulation. Thus, the promotion of endothelialization with EPO provides an additional therapeutic option for preventing the recurrence of ANs. Significance Erythropoietin (EPO) is involved in erythropoiesis and related conditions and is reported to enhance stem‐cell mobilization from bone marrow while elevating stem‐cell viability and function. In this study, EPO was also found to stimulate endothelial progenitor cells to induce the endothelialization of a coiled embolic aneurysm neck via vascular endothelial growth factor modulation. Endothelialization induction provides an additional therapeutic opportunity during vascular inner layer repair and remodeling. The results provide important information on the unique role EPO plays during vascular repair and remodeling.

Keywords

• Cerebral aneurysm
• Endothelialization
• Endothelial progenitor cells
• Erythropoietin