Pathological Circulating Factors in Moyamoya Disease.

Yao-Ching Fang,Chaur-Jong Hu,Yong-Kwang Tu,Ling-Fei Wei

doi:10.3390/ijms22041696

Yao-Ching Fang, Chaur-Jong Hu + Show 2 more

Open Access

https://doi.org/10.3390/ijms22041696

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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.

Highlights

Moyamoya disease (MMD) is a cerebrovascular disease associated with progressive vascular stenosis, occlusion of the internal carotid artery (ICA), and the formation of excessive, hazy, proximal collateral vessels, which are termed “Moyamoya vessels” [1]
The expression of VEGF receptors (VEGFRs)-2, which is the receptor responsible for endothelial development and vessel production [38], was found to be reduced in patients with MMD with more favorable collateral vessel formation. These results indicated that increased VEGFR-2 may facilitate abnormal vessel formation; blocking of VEGFR-2 could be a therapeutic target [15,38]
Higher cerebrospinal fluid (CSF) levels of basic fibroblast growth factor (bFGF) were observed in patients with MMD, and bFGF levels increased after neovascularization from indirect revascularization [16]. These findings indicate that bFGF could be involved in the pathological pathway in MMD and could be a predictor of the efficacy of surgery [17]

Summary

Introduction

Moyamoya disease (MMD) is a cerebrovascular disease associated with progressive vascular stenosis, occlusion of the internal carotid artery (ICA), and the formation of excessive, hazy, proximal collateral vessels, which are termed “Moyamoya vessels” [1]. These fragile, smoke-like vessels provide insufficient cerebral perfusion, causing various symptoms, such as ischemic or hemorrhagic stroke, seizure, cognitive impairment, and disability or death in both children and adults with MMD [2,3]. MMD has mostly been identified in East Asia, and the annual incidence is high in Japan, China, Taiwan, and Korea [4,5] This regional and ethnic characteristic was determined to be strongly associated with genetic factors [6]. Not all patients with MMD have the RNF213 variant, which indicates that the pathology of MMD is a complex pathway that includes genetic factors, environmental factors, and an innate angiogenetic capacity [10,11]

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Discussion

Conclusion