Vascular Remodeling in Moyamoya Angiopathy: From Peripheral Blood Mononuclear Cells to Endothelial Cells

Int J Mol Sci. 2020 Aug 11;21(16):5763. doi: 10.3390/ijms21165763.


The pathophysiological mechanisms of Moyamoya angiopathy (MA), which is a rare cerebrovascular condition characterized by recurrent ischemic/hemorrhagic strokes, are still largely unknown. An imbalance of vasculogenic/angiogenic mechanisms has been proposed as one possible disease aspect. Circulating endothelial progenitor cells (cEPCs) have been hypothesized to contribute to vascular remodeling of MA, but it remains unclear whether they might be considered a disease effect or have a role in disease pathogenesis. The aim of the present study was to provide a morphological, phenotypical, and functional characterization of the cEPCs from MA patients to uncover their role in the disease pathophysiology. cEPCs were identified from whole blood as CD45dimCD34+CD133+ mononuclear cells. Morphological, biochemical, and functional assays were performed to characterize cEPCs. A significant reduced level of cEPCs was found in blood samples collected from a homogeneous group of adult (mean age 46.86 ± 11.7; 86.36% females), Caucasian, non-operated MA patients with respect to healthy donors (HD; p = 0.032). Since no difference in cEPC characteristics and functionality was observed between MA patients and HD, a defective recruitment mechanism could be involved in the disease pathophysiology. Collectively, our results suggest that cEPC level more than endothelial progenitor cell (EPC) functionality seems to be a potential marker of MA. The validation of our results on a larger population and the correlation with clinical data as well as the use of more complex cellular model could help our understanding of EPC role in MA pathophysiology.

Keywords: Moyamoya angiopathy; RNF213; endothelial progenitor cells; neovascularization.

MeSH terms

  • Adult
  • Biomarkers / blood
  • Cell Count
  • Child
  • Cytokines / metabolism
  • Endothelial Cells / pathology*
  • Female
  • Gene Expression Regulation
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Leukocytes, Mononuclear / pathology*
  • Male
  • Moyamoya Disease / blood
  • Moyamoya Disease / genetics
  • Moyamoya Disease / physiopathology*
  • Neovascularization, Physiologic
  • Paracrine Communication
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Vascular Remodeling* / genetics


  • Biomarkers
  • Cytokines
  • RNA, Messenger