Common and Distinct Circulating MicroRNAs Across Four Neurovascular Disorders
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ABSTRACT:
PROVIDER: PRJNA1215254 | ENA |
REPOSITORIES: ENA
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Project description:Background: Familial cerebral cavernous malformations (FCCM), Sturge-Weber Syndrome (SWS), and hereditary hemorrhagic telangiectasia with brain arteriovenous malformations (HHT) are neurovascular disorders driven by genetic mutations. Cerebral microbleeds (CMBs) are primarily associated with the aging process with less known about genetic drivers. This study hypothesizes that common and distinct circulating microribonucleic acids (miRNAs) reflect shared and different pathobiology and can serve as potential diagnostic and mechanistic biomarkers. Methods: Common and unique differentially expressed (DE) plasma miRNAs (p<0.05, FDR corrected, absolute fold change [|FC|]>1.5]) were identified between patients with FCCM, SWS, HHT and CMB, compared to age- and sex-propensity-matched healthy subjects. Ingenuity Pathway Analysis as well as transcriptome integration analyses were performed to identify gene targets and their associated pathways. Preselected miRNAs were finally validated using ddPCR. Results: Eleven DE miRNAs were identified in FCCM, 40 in SWS, 41 in HHT, and 26 in CMB (p<0.05, FDR-corrected, [|FC|]>1.5]). Further analyses showed that 18 DE miRNAs were commonly dysregulated in any two of the studied neurovascular disorders. The PI3K-Akt and ROBO SLIT signaling pathways were identified across all four disorders. The plasma levels of four of the 18 miRNAs were further validated (p<0.05) using ddPCR. Conclusion: The common dysregulated miRNAs across neurovascular disorders reflect shared pathophysiological pathways, underscoring their potential as biomarkers and therapeutic targets. These findings pave the way for further exploration of these miRNAs, aiming at the clinical application for disease monitoring and therapeutic intervention.
2025-08-07 | GSE287906 | GEO
Project description: Not available
| S-EPMC12341739 | biostudies-literature
Project description:Infant Circulating MicroRNAs as Biomarkers of Effect in Fetal Alcohol Spectrum Disorders
| PRJNA689559 | ENA
Project description:Cerebral small vessel disease (SVD) is frequently comorbid with Alzheimer’s disease (AD) and vascular brain endothelial cells (BECs) are enriched for the expression of genes associated with AD genetic risk. However, the gene regulatory landscapes of neurovascular cells and their intersection with genetic risk for disease remains unexplored. Here we have generated gene regulomes for human BECs, mural cells and other brain cell types to show that AD heritability is primarily immune-related and that it shows modest enrichment in BECs. By contrast, genetic risk for SVD is enriched across cells of the neurovascular unit, including astrocytes. Enhancer-to-gene interactomes implicate amyloid processes in both AD and SVD, though the risk genes are mostly distinct for the two disorders. Motifs for putative partners of lineage transcription factors in microglia and BECs were enriched for AD and SVD variants at genes linked to disease pathways. Gene prioritization and enrichment analyses further identified potential repurposable drugs for AD. Our findings highlight novel regulatory mechanisms and therapeutic targets within the neurovascular system.
2025-10-23 | GSE299072 | GEO
Project description:We found four circulating miRNAs showing high levels in plasma of pregnant Japanese Black cows. Since these miRNAs are less affected by the measurement system due to hemolysis, it was suggested that they may be used as markers for early pregnancy diagnosis in cattle.
2021-06-26 | GSE178906 | GEO
Project description:Aim of the present study is to identify all circulating miRNAs that are modulated in patients with stroke, to select specific miRNAs to be used as disease biomarkers to improve both diagnosis and prognosis. Background. Stroke is the second-most common cause of death worldwide. The major factor limiting prognosis in patients affected by acute stroke is the very limited therapeutic window, so that most patients are not able receive the most successful treatments because of delays in diagnosis and to differentiate between ischemic and hemorrhagic etiology. Circulating levels of selected microRNAs (miRNAs) were found to be modulated both in animal experimental models and in patients with stroke, opening up new avenues for the identification of more effective and specific biomarkers to identify and risk-stratify stroke patients. Study aim. Aim of the present study is to identify all circulating miRNAs that are modulated in patients with stroke, to select specific miRNAs to be used as disease biomarkers to improve both diagnosis and prognosis. Methods. RNA was extracted from plasma samples using a commercial RNA extraction kit and quality of extracted material was assessed using a fluorometric electrophoretic assay (Agilent 4200 TapeStation, Santa Clara, CA, USA). MiRNA profiling was performed using the Affymetrix platform using GeneChip 4.0 (Thermo Fischer Scientific, Waltham, MA, USA). RT-PCR was performed using the Taqman protocol. MiRNA were chosen among those with the most relevant modulation between the groups. Results. Among the circulating miRNAs that were most down-regulated in stroke patients, we identified miR-3135b (20-fold, p<0.001), associated with vascular calcifications and heart failure; miR-1275 (18-fold, p=0.028), involved in cardiovascular atherosclerotic diseases and a sponge for circMAN2B2 in cancer; miR-4467 (13-fold, p=0.003), modulated in neurodegenerative diseases; and miR-7170 (7-fold, p<0.001). Among the circulating miRNAs that were most up-regulated in stroke patients, we identified miR-18a (35-fold, p=0.004), associated with stroke in the Framingham Cohort; the platelet-enriched miR-22-5p (24-fold, p=0.004), that is modulated in Huntington Disease; miR-199a (11-fold, p=0.012), a marker of brain microvascular injury and of stroke severity in rats, and miR-106b (10-fold, p=0.009), a regulator of neural stem-cell proliferation/differentiation whose level are modulated in patients with neurodegenerative diseases. Conclusions. Our results identified several circulating miRNAs that are down- of up-regulated in stroke patients. Among those with the most relevant differential expression, several miRNAs were identified that are known to play a role in the pathophysiology of neurovascular diseases, paving the way to a new class of smart pathophysiology-based biomarkers in stroke.
2025-03-28 | GSE255070 | GEO
Project description:Erucamide regulates retinal neurovascular crosstalk
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Project description:Purpose: Previous work has shown a sustained protective effect of levodopa (L-DOPA) on retinal function in early-stage diabetic retinopathy in humans. Here, we quantify neurovascular function, investigate the longevity of L-DOPA treatment for sustained retinal protection, and assess gene expression changes to identify underlying biology in a diabetic mouse model. Methods: After confirming retinal functional deficits in streptozotocin (STZ)-induced diabetic mice using electroretinogram (ERG) and optomotor response (OMR), control and diabetic mice were treated with: 1) L-DOPA/carbidopa for four weeks (continuous), 2) two weeks of L-DOPA/two weeks of washout, or 3) vehicle for four weeks. During the final two weeks of treatment, ERG and OMR testing was repeated and the vasodilative response to photic flicker stimulus was measured to evaluate neurovascular coupling. Following retinal extraction, bulk RNASeq analyses of differentially expressed genes (DEGs), weighted gene co-expression network analysis (WGCNA), and gene ontology (GO) were used to relate neurovascular functional protection with retinal gene expression. Results: L-DOPA treatment improved ERG oscillatory potential timing and OMR responses in diabetic mice, with improvements maintained during the washout period. Flicker-induced venule vasodilative response also showed sustained improvement in the diabetic L-DOPA washout group. DEGs in the diabetic retina were similar across L-DOPA treatment groups. WGCNA revealed that L-DOPA treated diabetic mice had specific gene modules associated with synapse function and cytoskeletal components that correlated with L-DOPA-induced retinal function protection. Conclusions: L-DOPA treatment restored and sustained protection of retinal neurovascular function in early-stage diabetic retinopathy in mice. These improvements in function were associated with transcriptional changes related to retinal synapse activity and cytoskeletal integrity.
2026-07-20 | GSE318897 | GEO
Project description:Brain aging is associated with neurovascular uncoupling, blood-brain barrier (BBB) dysfunction, neuroinflammation, and cognitive decline. Brain endothelial cells are essential for maintaining BBB integrity and neurovascular homeostasis and are enriched for the transcription factor Krüppel-like factor 4 (KLF4). Because endothelial KLF4 expression declines with aging, we investigated whether endothelial KLF4 depletion contributes to age-associated neurovascular dysfunction and neuropsychiatric impairment.
2026-05-28 | GSE333394 | GEO
Project description:Brain aging is associated with neurovascular uncoupling, blood-brain barrier (BBB) dysfunction, neuroinflammation, and cognitive decline. Brain endothelial cells are essential for maintaining BBB integrity and neurovascular homeostasis and are enriched for the transcription factor Krüppel-like factor 4 (KLF4). Because endothelial KLF4 expression declines with aging, we investigated whether endothelial KLF4 depletion contributes to age-associated neurovascular dysfunction and neuropsychiatric impairment.
2026-05-28 | GSE333397 | GEO