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.
Keywords: Angiogenesis, arteriogenesis, collateralization, endothelial progenitor cells, growth factors, interleukins,
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