Influence of Inflammatory Disease on the Pathophysiology of Moyamoya Disease and Quasi-moyamoya Disease

Abstract

Moyamoya disease is a unique cerebrovascular disease that is characterized by progressive bilateral stenotic alteration at the terminal portion of the internal carotid arteries. These changes induce the formation of an abnormal vascular network composed of collateral pathways known as moyamoya vessels. In quasi-moyamoya disease, a similar stenotic vascular abnormality is associated with an underlying disease, which is sometimes an inflammatory disease. Recent advances in moyamoya disease research implicate genetic background and immunological mediators, and postulate an association with inflammatory disease as a cause of, or progressive factor in, quasi-moyamoya disease. Although this disease has well-defined clinical and radiological characteristics, the role of inflammation has not been rigorously explored. Herein, we focused on reviewing two main themes: (1) molecular biology of inflammation in moyamoya disease, and (2) clinical significance of inflammation in quasi-moyamoya disease. We have summarized the findings of the former theme according to the following topics: (1) inflammatory biomarkers, (2) genetic background of inflammatory response, (3) endothelial progenitor cells, and (4) noncoding ribonucleic acids. Under the latter theme, we summarized the findings according to the following topics: (1) influence of inflammatory disease, (2) vascular remodeling, and (3) mechanisms gleaned from clinical cases. This review includes articles published up to February 2019 and provides novel insights for the treatment of the moyamoya disease and quasi-moyamoya disease.

Keywords: inflammation; macrophage; moyamoya disease.

Fig. 1

Conceptualized overview of the association between inflammation and angiogenesis. The regulatory roles of RNF213, pro-inflammatory cytokines, anti-inflammatory cytokines, PI3K/Akt pathway, HIF-1/NF-κB pathway, Wnt/β-catenin pathway, caveolin-1/ERK pathway, and angiogenic mediators are shown. Two major pathways are conceptualized: (1) anti-inflammatory cytokine pathway, and (2) pro-inflammatory cytokines pathway with RNF213.

Fig. 2

Schematic of the progression pattern of arterial stenosis in quasi-moyamoya disease. (A) The terminal portion of the ICA in normal artery. (B) The arterial diameter is reduced by constrictive remodeling as shown in moyamoya disease and a majority of quasi-moyamoya diseases. (C) In some types of quasi-moyamoya diseases, the intimal thickening is remarkable with limited vascular constriction.

Fig. 3

Conceptualized schema of the mechanisms involved in the inflammatory diseases associated with the moyamoya disease. One mechanism highlights the initiation pathway in which pro-inflammatory cytokines influence RNF213. The other mechanism indicates that anti-inflammatory or pro-inflammatory cytokines influence the angiogenetic mediators for acceleration or acute aggravation of the moyamoya disease.