Gene dysregulation in peripheral blood of moyamoya disease and comparison with other vascular disorders

Xing, Peng; Zhang, Zhengshan; Ye, Dong-Qing; Xing, Peiqi; Zou, Zheng-Xing; Lei, Hongxing; Duan, Lian

doi:10.1371/journal.pone.0221811

Cited by 18 publications

(21 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although there are still controversial results and the exact role of EPCs has not yet been conclusively clarified, many studies have demonstrated an intimate correlation between EPCs and the development of MA ( Table 4 ) [ 21 , 23 , 24 ]. Very recently, transcriptomic and metabolomic profiling approaches have been reported for discovering potential disease biomarkers in peripheral blood of MA patients [ 43 , 44 ]. Hur et al have first in vitro characterized early and late EPCs from a single MA patient, which shared some endothelial phenotypes but showed different morphology, proliferation rate, survival features, and gene expression profiles.…”

Section: Discussionmentioning

confidence: 99%

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

Tinelli

Nava

Arioli

et al. 2020

IJMS

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

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

Tinelli

Nava

Arioli

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…Although there was no solid evidence showing the direct pathological relationship between the GZMB under expression and the occurrence of CAD and RA, we have identified some diseases linked to GZMB and correlated with CAD and RA. For example, CAD was found to be correlated with Moyamoya Disease (MDD) (Peng et al, 2019), and pneumonia (Garcia-Laorden et al, 2016). Furthermore, Xing Peng et al discovered that MDD patients with downregulated GZMB were also enriched with the downregulated genes of CAD (Peng et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…For example, CAD was found to be correlated with Moyamoya Disease (MDD) (Peng et al, 2019), and pneumonia (Garcia-Laorden et al, 2016). Furthermore, Xing Peng et al discovered that MDD patients with downregulated GZMB were also enriched with the downregulated genes of CAD (Peng et al, 2019). Many other studies also supported a correlation between MDD and CAD (Livesay & Johnson, 2019; Nam et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

ReDisX: a Continuous Max Flow-based framework to redefine the diagnosis of diseases based on identified patterns of genomic signatures

Yip

Chowdhury

Wang

et al. 2022

Preprint

View full text Add to dashboard Cite

Diseases originate at the molecular-genetic layer, manifest through altered biochemical homeostasis, and develop symptoms later. Hence symptomatic diagnosis is inadequate to explain the underlying molecular-genetic abnormality and individual genomic disparities. The current trends include molecular-genetic information relying on algorithms to recognize the disease subtypes through gene expressions. Despite their disposition toward disease-specific heterogeneity and cross-disease homogeneity, a gap still exists to describe the extent of homogeneity within the heterogeneous subpopulation of different diseases. They are limited to obtaining the holistic sense of the whole genome-based diagnosis resulting in inaccurate diagnosis and subsequent management. To fill those gaps, we proposed ReDisX framework, a scalable machine learning algorithm that uniquely classifies patients based on their genomic signatures. It was deployed to re-categorizes the patients with rheumatoid arthritis and coronary artery disease. It reveals heterogeneous subpopulations within a disease and homogenous subpopulations across different diseases. Besides, it identifies GZMB as a subpopulation-differentiation marker that plausibly serves as a prominent indicator for GZMB-targeted drug repurposing. The ReDisX framework offers a novel strategy to redefine disease diagnosis through characterizing personalized genomic signatures. It may rejuvenate the landscape of precision and personalized diagnosis, and a clue to drug repurposing.

show abstract

“…A total of 533 differentially expressed genes (DEGs) were identified for MMD. Up-regulated genes were mainly involved in ECM organization, whereas downregulated genes were primarily associated with inflammatory and immune responses [ 113 ]. Rare de novo copy number variation (CNV) screening was performed by Aloui et al in 13 MMD trios using whole exome sequencing (WES) read depth data and whole genome high density SNP array data.…”

Section: Genetic Association Studies and Sequencingmentioning

confidence: 99%

The Genetic Basis of Moyamoya Disease

Mertens

Graupera

Gerhardt

et al. 2021

Transl. Stroke Res.

View full text Add to dashboard Cite

Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by progressive spontaneous bilateral occlusion of the intracranial internal cerebral arteries (ICA) and their major branches with compensatory capillary collaterals resembling a “puff of smoke” (Japanese: Moyamoya) on cerebral angiography. These pathological alterations of the vessels are called Moyamoya arteriopathy or vasculopathy and a further distinction is made between primary and secondary MMD. Clinical presentation depends on age and population, with hemorrhage and ischemic infarcts in particular leading to severe neurological dysfunction or even death. Although the diagnostic suspicion can be posed by MRA or CTA, cerebral angiography is mandatory for diagnostic confirmation. Since no therapy to limit the stenotic lesions or the development of a collateral network is available, the only treatment established so far is surgical revascularization. The pathophysiology still remains unknown. Due to the early age of onset, familial cases and the variable incidence rate between different ethnic groups, the focus was put on genetic aspects early on. Several genetic risk loci as well as individual risk genes have been reported; however, few of them could be replicated in independent series. Linkage studies revealed linkage to the 17q25 locus. Multiple studies on the association of SNPs and MMD have been conducted, mainly focussing on the endothelium, smooth muscle cells, cytokines and growth factors. A variant of the RNF213 gene was shown to be strongly associated with MMD with a founder effect in the East Asian population. Although it is unknown how mutations in the RNF213 gene, encoding for a ubiquitously expressed 591 kDa cytosolic protein, lead to clinical features of MMD, RNF213 has been confirmed as a susceptibility gene in several studies with a gene dosage-dependent clinical phenotype, allowing preventive screening and possibly the development of new therapeutic approaches. This review focuses on the genetic basis of primary MMD only.

show abstract

Gene dysregulation in peripheral blood of moyamoya disease and comparison with other vascular disorders

Cited by 18 publications

References 76 publications

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

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

ReDisX: a Continuous Max Flow-based framework to redefine the diagnosis of diseases based on identified patterns of genomic signatures

The Genetic Basis of Moyamoya Disease

Contact Info

Product

Resources

About