Transplantation of autologous endothelial progenitor cells promotes the repair of fusiform aneurysms.

Abstract

Endothelial progenitor cells (EPCs), which are precursors for endothelial cells, possess the capability of repairing vascular damage and predicting the extent of early vascular injury. However, the role of EPCs in the repair of fusiform aneurysms is not clear. Here, we constructed a fusiform aneurysm model using pancreatic elastase digestion and validated the improvement effect of EPCs through histological staining and immunofluorescence. HE staining and elastic fiber staining showed destruction of the tunica adventitia in the fusiform aneurysm, marked dilatation of the arterial lumen, and thinning of the elastic lamina in the fusiform aneurysm. In the fusiform aneurysm group, the concentration of vascular endothelial growth factor (VEGF) was notably decreased compared to both the control and the saline group. The level of EPCs in the peripheral blood was decreased in the model group. Transplantation of EPCs into fusiform aneurysms promoted vascular repair, indicated by the decrease of myeloperoxidase (MPO), advanced oxidation protein products (AOPP), matrix metalloproteinase-9 (MMP-9), platelet factor 4 (PF4), and Fe²⁺. The level of VEGF was also elevated after EPCs transplantation. Finally, we noted a marked rise in lactate level in the peripheral blood of fusiform aneurysms. Lactate treatment led to an elevation of H3K18la levels in EPCs and inhibited cell proliferation. In conclusion, this study discovered that in mice with fusiform aneurysms, elevated lactate levels in the peripheral blood trigger histone lactylation, such impeding the proliferation of EPCs. Transplantation of EPCs into fusiform aneurysms facilitated aneurysm repair. These findings lay the groundwork for EPCs in the treatment of fusiform aneurysms.