Pathological Circulating Factors in Moyamoya Disease

Abstract

Moyamoya disease (MMD) is a cerebrovascular disease that presents with vascular stenosis and a hazy network of collateral formations in angiography. However, the detailed pathogenic pathway remains unknown. Studies have indicated that in addition to variations in the of genetic factor RNF213, unusual circulating angiogenetic factors observed in patients with MMD may play a critical role in producing "Moyamoya vessels". Circulating angiogenetic factors, such as growth factors, vascular progenitor cells, cytokines, inflammatory factors, and other circulating proteins, could promote intimal hyperplasia in vessels and excessive collateral formation with defect structures through endothelial hyperplasia, smooth muscle migration, and atypical neovascularization. This study summarizes the hypothesized pathophysiology of how these circulating factors affect MMD and the interactive modulation between them.

Keywords: Moyamoya disease; RNF213; cerebrovascular disease; circulating factor; collateral formations; growth factors.

Figure 1

Various circulating factors interact, engendering endothelial proliferation, smooth muscle cell (SMC) proliferation, and migration. These effects result in excessive but defective neovascularization, which causes intimal thickening and occlusion and compensatory atypical collateral formation, both of which are characteristics of Moyamoya disease (MMD). HIF, hypoxia-inducible factor; HGF, hepatocyte growth factor; bFGF, basic fibroblast growth factor; PDGF, platelet-derived growth factor; VEGF, vascular endothelial growth factor; Cav-1, caveolin-1; TGF-β1, transforming growth factor; IL-1β, interleukin-1β; IgG, immunoglobin G; EPC, endothelial progenitor cell; SPC, smooth muscle progenitor cell; CRABP-1, cellular retinoic acid binding protein; MCP-1, monocytes chemoattractant protein-1; MMP-9, matrix metalloproteinase 9.).