The Pathogenetic Mechanism for Moyamoya Vasculopathy Including a Possible Trigger Effect of Increased Flow Velocity

Abstract

Moyamoya disease (MMD), which commonly exhibits moyamoya vasculopathy characterized by chronic progressive steno-occlusive lesions in the circle of Willis with "moyamoya" collateral vessels, has been well known for its unique demographic and clinical features. Although the discovery of the susceptibility gene RNF213 for MMD revealed the factor for its predominance in East Asians, the mechanisms underlying other predominant conditions (females, children, young to middle-aged adults, and anterior circulation) and lesion formation are yet to be determined. As MMD and moyamoya syndrome (MMS), which secondarily produces moyamoya vasculopathy due to pre-existing diseases, have the same vascular lesions despite differences in their original pathogenesis, they may share a common trigger for the development of vascular lesions. Thus, we herein consider a common trigger from a novel perspective on blood flow dynamics. Increased flow velocity in the middle cerebral arteries is an established predictor of stroke in sickle cell disease, which is often complicated by MMS. Flow velocity is also increased in other diseases complicated by MMS (Down syndrome, Graves' disease, irradiation, and meningitis). In addition, increased flow velocity occurs under the predominant conditions of MMD (females, children, young to middle-aged adults, and anterior circulation), suggesting a relationship between flow velocity and susceptibility to moyamoya vasculopathy. Increased flow velocity has also been detected in the non-stenotic intracranial arteries of MMD patients. In a pathogenetic overview of chronic progressive steno-occlusive lesions, a novel perspective including the trigger effect of increased flow velocity may provide insights into the mechanisms underlying their predominant conditions and lesion formation.

Keywords: Increased flow velocity; Moyamoya disease; Moyamoya syndrome; Moyamoya vasculopathy; Pathogenetic mechanism.

Figure 1.

Vascular biological considerations for increased flow velocity in the development of steno-occlusive negative remodeling. An increase in flow velocity may activate a vicious circle of elevated shear stress, the upregulation of endothelin-1, and vasoconstriction with the proliferation of smooth muscle cells.

Figure 2.

A comprehensive view of pathogenetic mechanisms underlying vascular lesions of MMD.