Pathophysiology and genetic factors in moyamoya disease

Abstract

<jats:p>Moyamoya disease is an uncommon cerebrovascular condition characterized by progressive stenosis of the bilateral internal carotid arteries with compensatory formation of an abnormal network of perforating blood vessels providing collateral circulation.</jats:p> <jats:p>The etiology and pathogenesis of moyamoya disease remain unclear. Evidence from histological studies, proteomics, and endothelial progenitor cell analyses suggests new theories underlying the cause of vascular anomalies, including moyamoya disease.</jats:p> <jats:p>Familial moyamoya disease has been noted in as many as 15% of patients, indicating an autosomal dominant inheritance pattern with incomplete penetrance. Genetic analyses in familial moyamoya disease and genome-wide association studies represent promising strategies for elucidating the pathophysiology of this condition.</jats:p> <jats:p>In this review, the authors discuss recent studies that have investigated possible mechanisms underlying the etiology of moyamoya disease, including stem cell involvement and genetic factors. They also discuss future research directions that promise not only to offer new insights into the origin of moyamoya disease but to enhance our understanding of new vessel formation in the CNS as it relates to stroke, vascular anomalies, and tumor growth.</jats:p>

Review of Past Research and Current Concepts on the Etiology of Moyamoya Disease

“…None, for example, can answer the simple question of whether or not the primary lesions of moyamoya disease are localized to the terminal portion of the internal carotid artery. 1,35,49,62,63) Probably some studies, such as those of the abnormal value of cytokines, may reflect the secondary phenomena accompanying moyamoya disease rather than its essential cause. In addition, some phenomena, such as infection and HLA alleles abnormality, may be correlated to some trigger or enhancer of the disease.…”

“…1,14,37,52,73) Evidence for a genetic contribution to moyamoya disease is suggested by strong regional differences with a high occurrence in Asian countries (primarily Japan and Korea) and much smaller rates in Western countries, as well as with many familial occurrences and high incidence in concordant monozygotic twins. 12,37,50,52) Further evidence shows that the female to male ratio rises from 1.6:1 in sporadic cases to 5.0:1 in familial cases; and the mean age of onset drops from 30.0 years in sporadic cases to 11.8 years in familial cases.…”

A genome-wide association study identifies RNF213 as the first Moyamoya disease gene

“…4 Growing attention has been paid to the upregulation of arteriogenesis and angiogenesis associated with MMD because chronic ischemia in other disease conditions is not always associated with a massive development of collateral vessels. 5,6 Several angiogenic growth factors are thought to have functions in the development of MMD. 7 Several lines of evidence support the importance of genetic factors in susceptibility to MMD.…”

Sonographic findings associated with stenosis progression and vascular complications in moyamoya disease

“…In the sonographic analyses, the MWSSVs were 12.3 ± 8.5 dyne/cm 2 for ICAs and 15.4 ± 9.7 dyne/cm 2 for MCAs, and the MWSSV for each hemisphere was 13.5 ± 7.3 dyne/ cm 2 (Tables 2 and 3). The Reynolds number ranged from 35.0 to 683.0, indicating that blood flows could be regarded as laminar.…”

“…8,16,25 Stenosis progression (SP) in patients with MMD occurs frequently. 17 Various factors regarding vascular remodeling, including matrix metalloproteinases (MMPs) and their natural inhibitors (tissue inhibitors of metalloproteinases [TIMPs]), are known to be altered in MMD, 2,5,8,13,14,16,19,25,30 implying that dysregulation of the vascular remodeling response to various stressors could be the mechanism of SP. ) was defined as the shear rate multiplied by blood viscosity.…”