Endothelial Progenitor Cells Induce Angiogenesis: A Potential Mechanism Underlying Neovascularization in Encephaloduroarteriosynangiosis

Abstract

Background and purpose: Encephaloduroarteriosynangiosis (EDAS) is one of the most commonly used indirect vascular reconstruction methods. EDAS aids in the formation of collateral vessels from the extracranial to the intracranial circulation in patients with moyamoya disease (MMD). However, the underlying mechanism of collateral vessel formation is not well understood. Endothelial progenitor cells (EPCs) differentiate to form the vascular endothelial cells and play a very important role in angiogenesis. We designed this prospective clinical trial to investigate the presence of EPCs in patients with MMD and to explore the neovascularization mechanism mediated by the EPCs in EDAS. Materials and Methods: The patients who were diagnosed with MMD were recruited between February 5, 2017 and January 7, 2018. The blood samples were obtained from an antecubital vein and were analyzed using flow cytometry. EPCs were defined as CD34brCD133+CD45dimKDR+. All the patients enrolled in the study underwent EDAS. Cerebral arteriography was performed 6 months post-EDAS to assess the efficacy of synangiosis. The correlation between EPC count and good collateral circulation was evaluated. Result: Among the 116 patients with MMD enrolled in this study, 73 were women and 43 were men. The average age of the patients was 33.8 ± 15.2 years. The EPC count of the patients with MMD was 0.071% ± 0.050% (expressed as percentage of the peripheral blood mononuclear cells). The EPC count in the good postoperative collateral circulation group was significantly higher (0.085% ± 0.054%) than that in the poor collateral circulation group (0.048% ± 0.034%) (P = 0.000). The age, modified Suzuki-Mugikura grade, and EPC count were significantly correlated with the good collateral circulation post-EDAS in the multivariate analysis (P = 0.018, P = 0.007, and P = 0.003, respectively). Conclusions: The formation of collateral vessels by EDAS is primarily driven by angiogenesis. The EPC count may be the most critical factor for collateral circulation. The therapeutic effect of EDAS is more likely to benefit younger or severe ischemic patients with MMD. Funding: This study was supported by grant from the National Natural Science Foundation of China (Grant Nos. 81571136) and Beijing Municipal Science & Technology Commission No.Z171100001017144). Declaration of Interest: None. Ethical Approval: The study was approved by the Research Ethics Board at the Fifth Medical Center of Chinese PLA General Hospital and all the subjects provided a written informed consent to participate in the study. All the procedures performed in this study involving human participants were in accordance with the Declaration of Helsinki (1964). This study was registered at ClinicalTrials.gov (NCT03613701).