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.

An Interesting Case of Moyamoya Disease, a Rare Cause of Transient Ischemic Attacks

“…With 10% of the disease being familial, the strongest genetic association has been with the Ring factor 213 (RNF213) gene. Circulating endothelial progenitor cells, mainly responsible for neovascularization in postnatal physiology, have been known to increase in patients with MMD and decrease after revascularization procedure [7]. RNF213 was also associated with increased serum microRNAs that have multiple functions, including angiogenesis.…”

Moyamoya Disease: A Review of Current Literature

“…However, several mechanisms have been hypothesized. One such mechanism is that the presence of pro-inflammatory cytokines in addition to mutated RNF213 leads to increased angiogenesis [12]. The inability of mutated RNF213 to cause changes seen in MMD, without any added insults, was also indicated in an experiment.…”

Pathological Circulating Factors in Moyamoya Disease

“…Inflammatory responses promote intimal hyperplasia and neovascularization, causing stenosis/vessel occlusion and further collateral formation, both of which are observed in MMD. These relative proinflammatory and anti-inflammatory cytokines are mediated by immune cells, such as M2 macrophage and Treg cells, indicating that the pathology of MMD may be related to the immune-mediated inflammatory pathway [ 46 ] ( Table 1 ).…”

“…Although the dysfunctional intima and vessel stenosis caused by inflammation and immune activities appear to coincide with the characteristics observed in MMD, some studies have defined MMD as a noninflammatory disease, because no inflammatory cells or macrophage infiltration in the subintimal layer are identified. However, even if inflammatory responses do not cause the pathogenesis of MMD directly, they still affect RNF213 and promote curative angiogenesis [ 46 ].…”