Review of past and present research on experimental models of moyamoya disease

Hamauchi, Shuji; Shichinohe, Hideo; Houkin, Kiyohiro

doi:10.4103/2394-8108.166377

Cited by 8 publications

(5 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[ 11 ] However, the pathological features of MMD are distinct from those of atherosclerosis in that there is little macrophage infiltration or lipid deposition at the affected site. [ 50 ] Major pathological findings of the intimal lesions in MMD include fibrous thickening with minimal intracellular or extracellular lipid deposition, and minimal inflammatory cell infiltration without significant disruption of the internal elastic lamina. [ 51 – 53 ] Ikeda et al analyzed autopsy specimens from patients with MMD and showed that the extracranial vessels, including the coronary, pulmonary, renal, and pancreatic arteries, exhibited essentially the same intimal lesions as the intracranial vessels.…”

Section: Discussionmentioning

confidence: 99%

Significant association of RNF213 p.R4810K, a moyamoya susceptibility variant, with coronary artery disease

et al. 2017

View full text Add to dashboard Cite

BackgroundThe genetic architecture of coronary artery disease has not been fully elucidated, especially in Asian countries. Moyamoya disease is a progressive cerebrovascular disease that is reported to be complicated by coronary artery disease. Because most Japanese patients with moyamoya disease carry the p.R4810K variant of the ring finger 213 gene (RNF213), this may also be a risk factor for coronary artery disease; however, this possibility has never been tested.Methods and resultsWe genotyped the RNF213 p.R4810K variant in 956 coronary artery disease patients and 716 controls and tested the association between p.R4810K and coronary artery disease. We also validated the association in an independent population of 311 coronary artery disease patients and 494 controls. In the replication study, the p.R4810K genotypes were imputed from genome-wide genotyping data based on the 1000 Genomes Project. We used multivariate logistic regression analyses to adjust for well-known risk factors such as dyslipidemia and smoking habits. In the primary study population, the frequency of the minor variant allele was significantly higher in patients with coronary artery disease than in controls (2.04% vs. 0.98%), with an odds ratio of 2.11 (p = 0.017). Under a dominant model, after adjustment for risk factors, the association remained significant, with an odds ratio of 2.90 (95% confidence interval: 1.37–6.61; p = 0.005). In the replication study, the association was significant after adjustment for age and sex (odds ratio = 4.99; 95% confidence interval: 1.16–21.53; p = 0.031), although it did not reach statistical significance when further adjusted for risk factors (odds ratio = 3.82; 95% confidence interval: 0.87–16.77; p = 0.076).ConclusionsThe RNF213 p.R4810K variant appears to be significantly associated with coronary artery disease in the Japanese population.

show abstract

Section: Discussionmentioning

confidence: 99%

Significant association of RNF213 p.R4810K, a moyamoya susceptibility variant, with coronary artery disease

et al. 2017

View full text Add to dashboard Cite

show abstract

“…These 1069-target genes included genes known to be associated with MMD [ 3 , 4 , 27 ], such as RNF213, fibroblast growth factors (FGF2, 7, 14, and 17), hepatocyte growth factor (HGF), platelet derived growth factor B (PDGFB), tumor transforming growth factor beta receptors (TGFBR1 and 2), tumor necrosis factor superfamily member genes (TNFSF4 and 12), and vascular endothelial growth factor A (VEGF A). Notably, hsa-miR-6722-3p can regulate multiple MMD-related genes including RNF213, FGF2 (also known as basic FGF), insulin like growth factor 1 receptor (IGF1R), as well as kinase insert domain receptor (KDR, also known as VEGFR2).…”

Section: Resultsmentioning

confidence: 99%

Circulating miRNome profiling in Moyamoya disease-discordant monozygotic twins and endothelial microRNA expression analysis using iPS cell line

et al. 2018

Self Cite

View full text Add to dashboard Cite

BackgroundMoyamoya disease (MMD) is characterized by progressive stenosis of intracranial arteries in the circle of Willis with unknown etiology even after the identification of a Moyamoya susceptible gene, RNF213. Recently, differences in epigenetic regulations have been investigated by a case-control study in MMD. Here, we employed a disease discordant monozygotic twin-based study design to unmask potential confounders.MethodsCirculating genome-wide microRNA (miRNome) profiling was performed in MMD-discordant monozygotic twins, non-twin-MMD patients, and non-MMD healthy volunteers by microarray followed by qPCRvalidation, using blood samples. Differential plasma-microRNAs were further quantified in endothelial cells differentiated from iPS cell lines (iPSECs) derived from another independent non-twin cohort. Lastly, their target gene expression in the iPSECs was analyzed.ResultsMicroarray detected 309 plasma-microRNAs in MMD-discordant monozygotic twins that were also detected in the non-twin cohort. Principal component analysis of the plasma-microRNA expression level demonstrated distinct 2 groups separated by MMD and healthy control in the twin- and non-twin cohorts. Of these, differential upregulations of hsa-miR-6722-3p/− 328-3p were validated in the plasma of MMD (absolute log2 expression fold change (logFC) > 0.26 for the twin cohort; absolute logFC > 0.26, p < 0.05, and q < 0.15 for the non-twin cohort). In MMD derived iPSECs, hsa-miR-6722-3p/− 328-3p showed a trend of up-regulation with a 3.0- or higher expression fold change. Bioinformatics analysis revealed that 41 target genes of miR-6722-3p/− 328-3p were significantly down-regulated in MMD derived iPSECs and were involved in STAT3, IGF-1-, and PTEN-signaling, suggesting a potential microRNA-gene expression interaction between circulating plasma and endothelial cells.ConclusionsOur MMD-discordant monozygotic twin-based study confirmed a novel circulating microRNA signature in MMD as a potential diagnostic biomarker minimally confounded by genetic heterogeneity. The novel circulating microRNA signature can contribute for the future functional microRNA analysis to find new diagnostic and therapeutic target of MMD.Electronic supplementary materialThe online version of this article (10.1186/s12920-018-0385-3) contains supplementary material, which is available to authorized users.

show abstract

“…Understanding MMA is challenging and limited by the lack of specific in vivo and in vitro disease experimental models. Nevertheless, several preclinical in vivo or in vitro MMA models, including EPCs, smooth muscle cells (SMCs), iPSC, as well as RNF213-KO animal models, or more recently, surgical models, were established to improve our knowledge about disease drivers [12,13,[24][25][26]. Regarding the pathophysiology of ischemic cerebrovascular events, it has been demonstrated that endovascular thrombosis, together with hyperplasia of smooth muscle cells, leads to progressive stenosis or occlusion of the distal ICA [2].…”

Section: Pathophysiologymentioning

confidence: 99%

Clinical Management of Moyamoya Patients

Canavero

Vetrano

Zedde

et al. 2021

JCM

View full text Add to dashboard Cite

Moyamoya angiopathy (MMA) is a peculiar cerebrovascular condition characterized by progressive steno-occlusion of the terminal part of the internal carotid arteries (ICAs) and their proximal branches, associated with the development of a network of fragile collateral vessels at the base of the brain. The diagnosis is essentially made by radiological angiographic techniques. MMA is often idiopathic (moyamoya disease-MMD); conversely, it can be associated with acquired or hereditary conditions (moyamoya Syndrome-MMS); however, the pathophysiology underlying either MMD or MMS has not been fully elucidated to date, and this poor knowledge reflects uncertainties and heterogeneity in patient management. MMD and MMS also have similar clinical expressions, including, above all, ischemic and hemorrhagic strokes, then headaches, seizures, cognitive impairment, and movement disorders. The available treatment strategies are currently shared between idiopathic MMD and MMS, including pharmacological and surgical stroke prevention treatments and symptomatic drugs. No pharmacological treatment able to reverse the progressive disappearance of the ICAs has been found to date in both idiopathic and syndromic cases. Antithrombotic agents are usually prescribed in ischemic MMA, although the coexisting hemorrhagic risk should be considered. Surgical revascularization techniques, which are currently the best available treatment in symptomatic MMA, are associated with good long-term outcomes and reduced ischemic and hemorrhagic risks. Given the lack of dedicated randomized clinical trials, current treatment is mainly based on observational studies and physicians’ and surgeons’ expertise.

show abstract

Review of past and present research on experimental models of moyamoya disease

Cited by 8 publications

References 1 publication

Significant association of RNF213 p.R4810K, a moyamoya susceptibility variant, with coronary artery disease

Significant association of RNF213 p.R4810K, a moyamoya susceptibility variant, with coronary artery disease

Circulating miRNome profiling in Moyamoya disease-discordant monozygotic twins and endothelial microRNA expression analysis using iPS cell line

Clinical Management of Moyamoya Patients

Contact Info

Product

Resources

About