Fig. 5.

Three-route model of the hypothetical molecular pathology of moyamoya disease/syndrome. The model assumes that any of three independent abnormalities, endothelial dysfunction, smooth muscle cell dysfunction, and abnormal hemostasis, can lead to exaggerated proliferation of SMCs. Each abnormality can result in vascular stenosis. RNF213 R4810K is the major detrimental factor that elicits endothelial cell dysfunction. Pro-inflammatory signals such as IFNs can activate the transcription of RNF213