Numbers And Function Of Circulating Endothelial Progenitor Cells In Patients With Cerebral Aneurysms

Background and PurposeEndothelial dysfunction is one of the triggers for the formation of cerebral aneurysm (CA). The circulating endothelial progenitor cells (EPCs) play an important role in postnatal vasculogenesis and restoration of endothelial injury. Previous investigations illustrated that vascular endothelial growth factor (VEGF) can involve in the repairment and model of injuried vessel, which play a very important role in the formation and progression of CA. Therefore, we hypothesized that decreased number and impaired function of circulating EPCs was the key link of CA formation. Circulating EPCs and plasma VEGF are the two factors involved in the restoration of injuried vessel. The imbalance between circulating EPCs and plasma VEGF can contribute to the formation of immature vessel, which participates in the patholophysilogical process of CA formation.MethodsSixty-six patients with ruptured (n=35) and unruptured (n=21) CAs and 40 age-and-gender matched healthy control subjects were recruited. Blood circulating EPCs were identified by flow cytometry. The level of plasma vascular endothelial growth factor (VEGF) was measured by ELISA. Circulating EPCs from patients were cultured in vitro and the function of EPCs was evaluated by cell migration and senescence-associatedβ-galactosidase activity. In addition, we investigate the correlation between the percentages of EPC senescence and the counts of circulating endothelial progenitor cells in patients with CAs.Moreover, we retrospectively analysis the medication and clinical data of patients with CAs.ResultsThe number of circulating EPCs was significantly decreased in both unruptured and ruptured CAs patients (P＜0.05) compared with healthy control subjects. Impaired migratory capacity and elevated cellular senescence of cultured EPCs were observed in patients with CAs (P＜0.05). The percentages of EPC senescence in patients with CAs were negatively correlated (P＜0.05) with the numbers of circulating EPCs. In addition, there were higher levels of plasma VEGF in CA patients compared to healthy control subjects. Howere, there were no significant difference between unruptured and ruptured CAs patients (P＞0.05).Conclusions1. Reduced number and impaired function of circulating EPCs maybe the key link of the formation and progression of CAs.2. Circulating EPCs and plasma VEGF are the two important factors involved in the restoeration of injuried vessels. The imbalance between circulating EPCs and plasma VEGF play a very important role in the formation and progression of CAs.3. A novel hypothesis in the formation and progression of CAs has been proposed.4. Circulating EPCs may represent a novel therapeutic target for medical treatment and/or prevention for CAs.InnovationThis is the first clinical investigation showing that the numbers and functions of patients with cerebral aneurysm. In this study, we assess the role of circulating EPCs in the formation and progression of CAs. As a result, we propose a novel hypohesis on the formation and progression of CAs.