The Pathophysiology of Moyamoya Disease: An Update

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 called moyamoya vessels. Because the etiology of MMD is unknown, its diagnosis is based on characteristic angiographic findings. Re-vascularization techniques (e.g., bypass surgery) are used to restore perfusion, and are the primary treatment for MMD. 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. Genetic and environmental factors may play important roles in the development of the vascular stenosis and aberrant angiogenesis in complex ways. These factors include the related changes in circulating endothelial/smooth muscle 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. The possible strategies include targeting growth factors, retinoic acid, caveolin-1, and stem cells.

Keywords: Angiogenesis; Caveolin; Endothelial progenitor cells; Growth factors; Moyamoya disease.

Figure 1.

Potential mechanisms of moyamoya disease. The association between genetic, circulating, and environmental factors. RNF213, Ring finger 213; EPCs, endothelial progenitor cells; SPCs, smooth muscle progenitor cells; miRNAs, microRNAs; CRABP-1, cellular retinoic acid-binding protein-I.