Vasculogenic and Angiogenic Pathways in Moyamoya Disease

Curr Med Chem. 2016;23(4):315-45. doi: 10.2174/092986732304160204181543.


Background: Moyamoya disease (MMD) is a slowly progressing steno-occlusive cerebrovascular disease. The typical moyamoya vessels, which originate from an initial stenosis of the internal carotid, highlight that increased and/or abnormal angiogenic, vasculogenic and arteriogenic processes are involved in the disease pathophysiology.

Objective: Herein, we summarize the current knowledge on the most important signaling pathways involved in MMD vessel formation, particularly focusing on the expression of growth factors and function of endothelial progenitor cells (EPCs).

Methods and results: Higher plasma concentrations of vascular endothelial growth factor, matrix metalloproteinase, hepatocyte growth factor, and interleukin-1β were reported in MMD. A specific higher level of basic fibroblast growth factor was also found in the cerebrospinal fluid of these patients. Finally, the number and the functionality of EPCs were found to be increased. In spite of the available data, the approaches and findings reported so far do not give an evident correlation between the expression levels of the aforementioned growth factors and MMD severity. Furthermore, the controversial results provided by studies on EPCs, do not permit to understand the true involvement of these cells in MMD pathophysiology.

Conclusion: Further studies should thus be implemented to extend our knowledge on processes regulating both the arterial stenosis and the excessive formation of collateral vessels. Moreover, we suggest advances of integrated approaches and functional assays to correlate biological and clinical data, arguing for the development of new therapeutic applications for MMD.

Publication types

  • Review

MeSH terms

  • Animals
  • Blood Vessels / physiopathology*
  • Endothelial Progenitor Cells / pathology
  • Humans
  • Inflammation Mediators / metabolism
  • Moyamoya Disease / genetics
  • Moyamoya Disease / metabolism
  • Moyamoya Disease / pathology
  • Moyamoya Disease / physiopathology*
  • Neovascularization, Pathologic*


  • Inflammation Mediators