RNF213 and Circulating Factors in Patients with Moyamoya Disease

Abstract

Moyamoya disease (MMD) is a unique cerebrovascular disease characterized by the progressive stenosis of large intracranial arteries and a hazy network of basal collaterals. Because the etiology of MMD is unknown, the diagnosis of MMD is based on characteristic angiographic findings, and there is no specific treatment to prevent MMD progression. This review summarizes the recent advances in MMD pathophysiology, including the genetic and circulating factors related to disease development. Recently, the Ring finger 213 (RNF213) gene in the 17q25-ter region was identified as the susceptibility gene for MMD in East Asians. Although the exact function of RNF213 is unknown, the RNF213 genetic variant may be associated with the changes in circulating factors and the response to environmental factors. Such interactions of the RNF213 genetic variant with circulating factors or environmental factors may play important roles in the development of the vascular stenosis and aberrant angiogenesis in complex ways. Circulating factors include the related changes in circulating vascular progenitor cells, cytokines related to vascular remodeling and angiogenesis, and endothelium, such as caveolin which is a plasma membrane protein. With a better understanding of MMD pathophysiology, nonsurgical approaches targeting MMD pathogenesis may be available to stop or slow the progression of this disease in the future.