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.

RNF213 gene silencing upregulates transforming growth factor β1 expression in bone marrow‑derived mesenchymal stem cells and is involved in the onset of Moyamoya disease

“…The incidence of MMD in Japan has increased from 0.35 per 100,000 individuals in 1995 to 0.94 per 100,000 individuals in 2006( 4 ). MMD has mostly been reported to exhibit a high incidence in various East Asian populations, including Chinese, Japanese and Korean ( 5 ). Although basic studies, including those using genomic and proteomic approaches, have been performed, the precise etiology of MMD remains unclear.…”

Presurgical Magnetic Resonance Imaging Indicators of Revascularization Response in Adults With Moyamoya Vasculopathy

“…2,15 Due to the severe intracranial stenosis that occurs in the ICAs and distal segments of the anterior circulation, the VBAs may supply anterior brain regions through circuitous collateral flow pathways and may also provide an important route for circulating growth factors or other markers of ischemic stress which may play a fundamental role in neoangiogenesis. [16][17][18][19] Of additional interest, it remains unclear whether demographic parameters such as age, race, and gender might affect revascularization outcome. This is particularly important given the increasingly recognized North American moyamoya phenotype.…”

Clinical Management of Moyamoya Patients

“…Several mechanisms have been hypothesized, including inflammation, upregulation of angiogenic factors, and abnormalities of endothelial progenitor cells (EPCs). For a long time, anomalies in angiogenesis and vasculogenesis have been suggested as potential disease mechanisms since altered levels of cytokines, chemokines, and growth factors were detected in cerebrospinal fluid (CSF) and serum of MMA patients [5,[8][9][10][11][12][13][14][15]. Afterward, the association of MMA with several heritable conditions (i.e., Down syndrome, sickle cell disease, neurofibromatosis type 1), the high familial rate, and the strong linkage between the disease and variants of Ring Finger Protein 213 (RNF213) gene in East Asian patients strengthened the role of genetic factors in MMA pathogenesis [16][17][18].…”

“…Thus, the trend of research has drastically changed, and studies focusing on the biological effect of mutant RNF213 have been developed. However, probably all these pathways contribute to the disease pathophysiology, and MMA results from a complex mechanism in which acquired infectious, inflammatory, and flow dynamic conditions [8,9,19,20] may trigger the disease in genetically susceptible individuals through angiogenic and vasculogenic pathways abnormalities [5].…”