The Impact of Moyamoya Disease and RNF213 Mutations on the Spectrum of Plasma Protein and MicroRNA

Lee, Ming‐Jen; Fallen, Shannon; Zhou, Yong; Baxter, David; Scherler, Kelsey; Kuo, Meng-Fai; Wang, Kai

doi:10.3390/jcm8101648

Cited by 8 publications

(6 citation statements)

References 56 publications

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“…MA is frequent in East Asian countries, while rarely reported in Caucasians. The association of MA with genetic disorders, the high familial rate, and the strong linkage with variants of Ring Finger Protein 213 (RNF213)/Mysterin coding gene in East Asian patients strengthen the role of genetic factors in MA pathogenesis [8][9][10][11][12][13][14][15]. Several reports implicated RNF213 as a sensor for mitochondrial dysfunction, hypoxia, and inflammation [14,[16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Plasma Lipid Profiling Contributes to Untangle the Complexity of Moyamoya Arteriopathy

Dei

Carrozzini

Pollaci

et al. 2021

IJMS

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Moyamoya arteriopathy (MA) is a rare cerebrovascular disorder characterized by ischemic/hemorrhagic strokes. The pathophysiology is unknown. A deregulation of vasculogenic/angiogenic/inflammatory pathways has been hypothesized as a possible pathophysiological mechanism. Since lipids are implicated in modulating neo-vascularization/angiogenesis and inflammation, their deregulation is potentially involved in MA. Our aim is to evaluate angiogenic/vasculogenic/inflammatory proteins and lipid profile in plasma of MA patients and control subjects (healthy donors HD or subjects with atherosclerotic cerebrovascular disease ACVD). Angiogenic and inflammatory protein levels were measured by ELISA and a complete lipidomic analysis was performed on plasma by mass spectrometry. ELISA showed a significant decrease for MMP-9 released in plasma of MA. The untargeted lipidomic analysis showed a cumulative depletion of lipid asset in plasma of MA as compared to HD. Specifically, a decrease in membrane complex glycosphingolipids peripherally circulating in MA plasma with respect to HD was observed, likely suggestive of cerebral cellular recruitment. The quantitative targeted approach demonstrated an increase in free sphingoid bases, likely associated with a deregulated angiogenesis. Our findings indicate that lipid signature could play a central role in MA and that a detailed biomarker profile may contribute to untangle the complex, and still obscure, pathogenesis of MA.

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Section: Introductionmentioning

confidence: 99%

Plasma Lipid Profiling Contributes to Untangle the Complexity of Moyamoya Arteriopathy

Dei

Carrozzini

Pollaci

et al. 2021

IJMS

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show abstract

“…Anomalies in angiogenesis and vasculogenesis have been invoked as potential disease mechanisms due to the detection of altered levels of cytokines, chemokines, and growth factors in cerebrospinal fluid and sera of MA patients [ 2 , 9 ]. Conversely, the association of MA with genetic disorders, the high familial rate, and the strong association with variants of Ring Finger Protein 213 (RNF213 ) gene in East Asian patients strengthen the role of genetic factors in MA pathogenesis [ 10 , 11 , 12 , 13 , 14 ]. Overall, it is believed that MA results from a complex mechanism in which acquired infectious, inflammatory, and flow dynamic conditions may trigger the disease in genetic susceptible individuals through angiogenic and vasculogenic pathways abnormalities [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

Vascular Remodeling in Moyamoya Angiopathy: From Peripheral Blood Mononuclear Cells to Endothelial Cells

Tinelli

Nava

Arioli

et al. 2020

IJMS

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The pathophysiological mechanisms of Moyamoya angiopathy (MA), which is a rare cerebrovascular condition characterized by recurrent ischemic/hemorrhagic strokes, are still largely unknown. An imbalance of vasculogenic/angiogenic mechanisms has been proposed as one possible disease aspect. Circulating endothelial progenitor cells (cEPCs) have been hypothesized to contribute to vascular remodeling of MA, but it remains unclear whether they might be considered a disease effect or have a role in disease pathogenesis. The aim of the present study was to provide a morphological, phenotypical, and functional characterization of the cEPCs from MA patients to uncover their role in the disease pathophysiology. cEPCs were identified from whole blood as CD45dimCD34+CD133+ mononuclear cells. Morphological, biochemical, and functional assays were performed to characterize cEPCs. A significant reduced level of cEPCs was found in blood samples collected from a homogeneous group of adult (mean age 46.86 ± 11.7; 86.36% females), Caucasian, non-operated MA patients with respect to healthy donors (HD; p = 0.032). Since no difference in cEPC characteristics and functionality was observed between MA patients and HD, a defective recruitment mechanism could be involved in the disease pathophysiology. Collectively, our results suggest that cEPC level more than endothelial progenitor cell (EPC) functionality seems to be a potential marker of MA. The validation of our results on a larger population and the correlation with clinical data as well as the use of more complex cellular model could help our understanding of EPC role in MA pathophysiology.

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“…The cladogram showed that Streptococcaceae and Peptostreptococcaceae were enriched in patients with MMD, while Rhodospirillaceae, Alphaproteobacteria, and Mollicutes were sparse in those patients. It is interesting that increase of Lachnospiraceae (R. gnavus belongs to this family) and decrease of Alphaproteobacteria is caused by angiogenin 21 , which might be associated with upregulated angiogenesis in MMD 22 . Angiogenesis and vasculogenesis manifested in patients with MMD, e.g., basal moyamoya, periventricular anastomosis, and leptomeningeal anastomosis, are regarded as compensation of the stenosis of the main trunk of the internal carotid arteries.…”

Section: Discussionmentioning

confidence: 99%

Increased abundance of Ruminococcus gnavus in gut microbiota is associated with moyamoya disease and non-moyamoya intracranial large artery disease

Mineharu

Nakamura

Sato

et al. 2022

Sci Rep

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Moyamoya disease (MMD) is a rare cerebrovascular disease endemic in East Asia. The p.R4810K mutation in RNF213 gene confers a risk of MMD, but other factors remain largely unknown. We tested the association of gut microbiota with MMD. Fecal samples were collected from 27 patients with MMD, 7 patients with non-moyamoya intracranial large artery disease (ICAD) and 15 control individuals with other disorders, and 16S rRNA were sequenced. Although there was no difference in alpha diversity or beta diversity between patients with MMD and controls, the cladogram showed Streptococcaceae was enriched in patient samples. The relative abundance analysis demonstrated that 23 species were differentially abundant between patients with MMD and controls. Among them, increased abundance of Ruminococcus gnavus > 0.003 and decreased abundance of Roseburia inulinivorans < 0.002 were associated with higher risks of MMD (odds ratio 9.6, P = 0.0024; odds ratio 11.1, P = 0.0051). Also, Ruminococcus gnavus was more abundant and Roseburia inulinivorans was less abundant in patients with ICAD than controls (P = 0.046, P = 0.012). The relative abundance of Ruminococcus gnavus or Roseburia inulinivorans was not different between the p.R4810K mutant and wildtype. Our data demonstrated that gut microbiota was associated with both MMD and ICAD.

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The Impact of Moyamoya Disease and RNF213 Mutations on the Spectrum of Plasma Protein and MicroRNA

Cited by 8 publications

References 56 publications

Plasma Lipid Profiling Contributes to Untangle the Complexity of Moyamoya Arteriopathy

Plasma Lipid Profiling Contributes to Untangle the Complexity of Moyamoya Arteriopathy

Vascular Remodeling in Moyamoya Angiopathy: From Peripheral Blood Mononuclear Cells to Endothelial Cells

Increased abundance of Ruminococcus gnavus in gut microbiota is associated with moyamoya disease and non-moyamoya intracranial large artery disease

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