Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Loss of soluble guanylate cyclase, the major nitric oxide receptor, leads to moyamoya and achalasia.

ABSTRACT: Background: Moyamoya is a cerebrovascular condition of unknown mechanism characterized by a progressive stenosis of the terminal part of the internal carotid arteries (ICA) and the compensatory development of abnormal “moyamoya” vessels. It leads to ischemic and hemorrhagic stroke. We describe a novel autosomal recessive disease leading to severe moyamoya and early onset achalasia and report its cause in 3 unrelated families. Methods: We used a combination of genetic linkage and exome sequencing in 2 consanguineous to identify rare shared variants. Sanger sequencing of GUCY1A3, the sole gene mutated in both families, was then conducted in the third family. Platelets from one of the patients and controls were used to carry out functional studies. Results: Homozygous mutations of GUCY1A3 gene encoding the alpha1 subunit of soluble guanylate cyclase (sGC), the major receptor for Nitric Oxide (NO), were identified in all 3 families. Platelet analysis showed a complete loss of the mutated protein and showed an unexpected stimulatory role of sGC within platelets. Conclusion: The NO/sGC/cGMP pathway is a major pathway controlling vascular smooth muscle (VSMC) relaxation, vascular tone and vascular remodeling. Our data suggest that alterations of this pathway may lead to an abnormal vascular remodeling process in sensitive vascular areas with low blood

ORGANISM(S): Homo sapiens

PROVIDER: GSE48099 | GEO | 2014/06/19

SECONDARY ACCESSION(S): PRJNA208928

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Loss of soluble guanylate cyclase, the major nitric oxide receptor, leads to moyamoya and achalasia.

Project description:Background: Moyamoya is a cerebrovascular condition of unknown mechanism characterized by a progressive stenosis of the terminal part of the internal carotid arteries (ICA) and the compensatory development of abnormal “moyamoya” vessels. It leads to ischemic and hemorrhagic stroke. We describe a novel autosomal recessive disease leading to severe moyamoya and early onset achalasia and report its cause in 3 unrelated families. Methods: We used a combination of genetic linkage and exome sequencing in 2 consanguineous to identify rare shared variants. Sanger sequencing of GUCY1A3, the sole gene mutated in both families, was then conducted in the third family. Platelets from one of the patients and controls were used to carry out functional studies. Results: Homozygous mutations of GUCY1A3 gene encoding the alpha1 subunit of soluble guanylate cyclase (sGC), the major receptor for Nitric Oxide (NO), were identified in all 3 families. Platelet analysis showed a complete loss of the mutated protein and showed an unexpected stimulatory role of sGC within platelets. Conclusion: The NO/sGC/cGMP pathway is a major pathway controlling vascular smooth muscle (VSMC) relaxation, vascular tone and vascular remodeling. Our data suggest that alterations of this pathway may lead to an abnormal vascular remodeling process in sensitive vascular areas with low blood A total of 17 samples (8 affected and 9 unaffected) were used for this study. Linkage analysis was performed in a single informative consanguine family composed of 2 unaffected parents, 4 affected siblings and 3 unaffected siblings. Two affected samples in two different families were used for the exome sequencing analysis and results were compared to 20 control exomes (in-house exomes from IntegraGen, Evry, France) and 8 HapMap exomes. All samples were used for Sanger Sequencing confirmation.

2014-06-19 | E-GEOD-48099 | biostudies-arrayexpress

miRNA expression in cerebrospinal fluid with moyamoya disease

Project description:We performed microarray analysis to determine the expression profiles of miRNAs in cerebrospinal fluid with moyamoya disease

2020-04-03 | GSE129792 | GEO

Treatment effects of soluble guanylate cyclase modulation on diabetic kidney disease at single-cell resolution

Project description:Diabetic kidney disease (DKD) is the most common cause of renal failure. Therapeutics development is hampered by our incomplete understanding of animal models on a cellular level. We show that ZSF1 rats recapitulate human DKD on a phenotypic and transcriptomic level. Tensor decomposition prioritizes proximal tubule (PT) and stroma as phenotype-relevant cell types exhibiting a continuous lineage relationship. As DKD features endothelial dysfunction, oxidative stress, and nitric oxide depletion, soluble guanylate cyclase (sGC) is a promising DKD drug target. sGC expression is specifically enriched in PT and stroma. In ZSF1 rats, pharmacological sGC activation confers considerable benefits over stimulation and is mechanistically related to improved oxidative stress regulation, resulting in enhanced downstream cGMP effects. Finally, we define sGC gene co-expression modules, which allow stratification of human kidney samples by DKD prevalence and disease-relevant measures such as kidney function, proteinuria, and fibrosis, underscoring the relevance of the sGC pathway to patients.

2023-02-24 | GSE209821 | GEO

Vascular smooth muscle cell derived from iPS cell of Moyamoya disease - Comparative characterization with endothelial cell transcriptome

Project description:Transcriptome analysis of vascular smooth muscle cells differentiated from iPS-derived neural crest stem cells in Moyamoya disease Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by steno-occlusive changes in the cerebral arteries at the base of the brain with unknown etiology, although histopathological features have demonstrated as fibrocellular thickening of the intima and medial thinning on the steno-occlusive arteries. However, the pathophysiology of proliferating cells in the thickened intima is still obscure. Furthermore, biological features of the vascular smooth muscle cells are unclear in MMD. Here, we aimed to analyze whole genome gene expression profile in VSMC using induced pluripotent stem (iPS) cell line. We generated iPS cell line from the blood of MMD with RNF213 R4810K risk allele (rs112735431) or healthy control without the risk allele. VSMCs were differentiated from iPS-derived neural crest stem cells. As a result, we successfully established cranio-cervical region specific VSMC confirmed by immunocytochemistry. Biological cellular features, including cellular proliferation, migration, and contraction ability were similar in VSMCs between MMD and control. Genome-wide gene expression analysis showed similar transcriptome profile in the VSMCs between MMD and control. Differential gene expression analysis in MMD-VSMC revealed 6 differentially expressed genes (4 upregulated, 2 down regulated in MMD), including decorin (DCN, upregulated in MMD), playing an inhibitory role in angiogenesis. In conclusion, VSMCs are not impaired in cellular function with similar transcriptome profile in MMD compared to healthy control. Since many previous studies have shown impaired EC features in MMD, our study suggests EC may play more role in the vascular pathogenesis in MMD rather than VSMC.

2020-09-11 | GSE131293 | GEO

Determination of the serum miRNA expression profile in human moyamoya disease (MMD)

2013-04-04 | GSE45737 | GEO

Determination of the serum miRNA expression profile in human moyamoya disease (MMD)

Project description:Moyamoya disease (MMD) is a cerebrovascular disease characterized by progressive stenosis of the intracranial internal carotid arteries and their proximal branches. However, the etiology of this rare disease remains widely unknown. Serum microRNA (miRNA) profiles have been screened to identify novel biomarkers for disease diagnosis and prognosis. Here, we identified important serum miRNAs that might play important roles in contributing to MMD pathogenesis through microarray analysis. 10 MMD patients and 10 controls were consecutively recruited at Shanghai Changhai Hospital. Five-ml venous blood was collected from each participant and separated into serum and cellular fractions. We pooled serum samples from 10 MMD patients and 10 controls. Agilent Human 8 x 60K miRNA Array was performed on the two pooled samples.

2013-04-04 | E-GEOD-45737 | biostudies-arrayexpress

MiRNA sequencing for CSF-derived EVs microRNAs in patients with moyamoya disease and arteriosclerotic cerebral ischemia

Project description:We aimed to clarify what specific changes occur in the expression level of extracellular vesicles (EVs) -derived microRNAs (miRNAs) in intracranial cerebrospinal fluid (CSF) in moyamoya disease. Patients with arteriosclerotic cerebral ischemia were used as controls to eliminate the effects of cerebral ischemia. Comprehensive expression analysis of miRNAs extracted from EVs by the next-generation sequencer was performed.

2022-04-22 | GSE193012 | GEO

MiRNA expression in cerebrospinal fluid of angiogenesis or non-angiogenesis after Encephalo-myo-synangiosis in patients with moyamoya disease

Project description:At present, the treatment for moyamoya disease (MMD) primarily consists of combined direct and indirect bypass surgery. Nevertheless, more than half of indirect bypass surgeries fail to develop good collaterals from the dura and temporal muscle. This study aimed to investigate whether microRNAs (miRNAs) in cerebrospinal fluid (CSF) could serve as biomarkers for the prediction of postoperative collateral formation.

2021-07-14 | GSE168469 | GEO

Plasma Exosomal Proteomic Analysis between Moyamoya Disease and Intracranial Atherosclerotic Disease.

Project description:Moyamoya disease (MMD) and atherosclerosis (ICAD) are both common causes of chronic intracranial vascular occlusion. Surgical revascularization is the preferred procedure for MMD but is not recommended for ICAD, and may be related to vascular reserve capacity, however, the precise reason is not fully understood. Previous studies showed exosomes could regulate revascularization, so we hypothesize plasma exosomal proteins play critical roles in MMD during revascularization. Quantitative proteomics technique and bioinformatics method were used to identify potential key plasma exosomal proteins for revascularization in MMD.

2022-04-27 | PXD033463 |

miRNA expression in cerebrospinal fluid with moyamoya disease

Project description:miRNA expression in cerebrospinal fluid with moyamoya disease

| PRJNA532836 | ENA